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27 results on '"Florian Ingelfinger"'

1. S257: CAR T CELLS AND THEIR IMMUNE ENVIRONMENT SHAPE DISTINCT IMMUNE PROFILES IN RESPONSE AND TOXICITY IN B CELL LYMPHOMA PATIENTS

Author: Stefanie Kreutmair, Maximilian Schaefer, Sebastian Stolz, Carla Merten, Can Ulutekin, Tobias Wertheimer, Florian Ingelfinger, Susanne Unger, Chiara Alberti, Aakriti Sethi, Markus Manz, Thorsten Zenz, Antonia Müller, Corinne Widmer, and Burkhard Becher
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2023
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2. S100A9 Drives the Chronification of Psoriasiform Inflammation by Inducing IL-23/Type 3 Immunity

Author: Bruno Marcel Silva de Melo, Flávio Protásio Veras, Pascale Zwicky, Diógenes Lima, Florian Ingelfinger, Timna Varela Martins, Douglas da Silva Prado, Stefanie Schärli, Gabriel Publio, Carlos Hiroji Hiroki, Paulo Henrique Melo, André Saraiva, Thainá Norbiato, Leonardo Lima, Bernhard Ryffel, Thomas Vogl, Johannes Roth, Ari Waisman, Helder I. Nakaya, Cacilda da Silva Souza, Fernando Q. Cunha, Thiago M. Cunha, Burkhard Becher, and José C. Alves-Filho
Subjects: Cell Biology, Dermatology, Molecular Biology, Biochemistry
Published: 2023

3. Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

Author: Florian Ingelfinger, Michael Kramer, Mirjam Lutz, Corinne C. Widmer, Luca Piccoli, Stefanie Kreutmair, Tobias Wertheimer, Mark Woodhall, Patrick Waters, Federica Sallusto, Antonio Lanzavecchia, Sarah Mundt, Burkhard Becher, and Bettina Schreiner
Subjects: Neurology, Neurology (clinical)
Abstract: Background and Objectives Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates. Methods We identified patients with acetylcholine receptor antibody–positive (AChR+) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses. We generated recombinant monoclonal antibodies (mAbs) corresponding to the B-cell receptors of the CLL phenotype B cells and screened them for autoantigen binding. Results A computational immune cell screen revealed a subgroup of 5/38 patients with MG and 0/21 healthy controls who displayed a CLL-like B-cell phenotype. In follow-up hematologic flow cytometry, 2 of these 5 patients were diagnosed with an MBL. An additional patient with AChR+ MG as a complication of manifest CLL presented at our neuromuscular clinic and was successfully treated with the anti-CD20 therapy obinutuzumab plus chlorambucil. We investigated the specificities of expanding CLL-like B-cell clones to assess a direct causal link between the 2 diseases. However, we observed no reactivity of the clones against the AChR, antigens at the neuromuscular junction, or other common autoantigens. Discussion Our study suggests that AChR autoantibodies are produced by nonmalignant, polyclonal B cells The new anti-CD20 treatment obinutuzumab might be considered in effectively treating AChR+ MG. Classification of Evidence This is a single case study and provides Class IV evidence that obinutuzumab is safe to use in patients with MG., Neurology: Neuroimmunology & Neuroinflammation, 10 (2), ISSN:2332-7812
Published: 2023
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4. Single-cell profiling of immune system alterations in lymphoid, barrier and solid tissues in aged mice

Author: Sinduya Krishnarajah, Florian Ingelfinger, Ekaterina Friebel, Dilay Cansever, Ana Amorim, Myrto Andreadou, David Bamert, Gioana Litscher, Mirjam Lutz, Maud Mayoux, Sarah Mundt, Frederike Ridder, Colin Sparano, Sebastian Anton Stifter, Can Ulutekin, Susanne Unger, Marijne Vermeer, Pascale Zwicky, Melanie Greter, Sonia Tugues, Donatella De Feo, and Burkhard Becher
Subjects: 0303 health sciences, 03 medical and health sciences, Aging, 0302 clinical medicine, Neuroscience (miscellaneous), Geriatrics and Gerontology, 030304 developmental biology, 030215 immunology
Published: 2021

5. B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis

Author: Can Ulutekin, Edoardo Galli, Mohsen Khademi, Ilaria Callegari, Fredrik Piehl, Nicholas Sanderson, Massimo Filippi, Roberto Furlan, Tomas Olsson, Tobias Derfuss, Florian Ingelfinger, and Burkhard Becher
Abstract: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Traditionally, MS was held to be a T-cell mediated disease, but accumulating evidence during the last decade also highlighted the crucial importance of B cells for the disease progression. Particularly, B cell depleting therapies (BCDTs), have demonstrated striking efficacy in suppressing inflammatory disease activity in relapsing-remitting MS. However, a detailed understanding of the role of B cells in the pathogenesis of MS is still lacking, and by extension also the mechanism of action of BCDTs. In this longitudinal multi-center study, we investigated the impact of BCDTs on the immune landscape in MS patients using high-dimensional single-cell immunophenotyping (cytometry by time-of-flight; CyTOF). Algorithm-guided analyses revealed phenotypic changes in the newly reconstituted B cell compartment after BCDT, as well as a marked specific reduction of circulating T follicular helper (Tfh) cells with a concomitant upregulation of CD27 surface expression in memory T helper cells and Tfh cells. These findings indicate a costimulatory mechanism in the CD27/CD70 signaling pathway, through which B cells sustain the activation of pathogenic T cells. Disrupting the CD27/CD70 signaling axis via BCDTs provides a potential explanation for its clinical efficacy.One Sentence SummaryB cell depletion contracts follicular T helper cells, displaces memory-to-naïve ratio and impairs CD27 signaling in T helper cells.
Published: 2022

6. Neuroprotective tissue adaptation induced by IL-12 attenuates CNS inflammation

Author: Myrto Andreadou, Florian Ingelfinger, Donatella De Feo, Ekaterina Friebel, Selma Tuzlak, Teresa M.L. Cramer, Bettina Schreiner, Pascale Eede, Shirin Schneeberger, Maria Geesdorf, Frederike Ridder, Christina Welsh, Daniel Kirschenbaum, Shiva K. Tyagarajan, Melanie Greter, Frank L. Heppner, Sarah Mundt, Burkhard Becher, and University of Zurich
Subjects: 10208 Institute of Neuropathology, 570 Life sciences, biology, 610 Medicine & health, 10263 Institute of Experimental Immunology
Abstract: IL-12 is a well-established driver of type 1 immune responses. Paradoxically, in several autoimmune conditions including neuroinflammation, IL-12 reduces pathology and exhibits regulatory properties. Yet, the mechanism and the involved cellular players behind this immune regulation remain elusive. To identify the IL-12-responsive elements which prevent immunopathology, we generated mouse models lacking a functional IL-12 receptor either in all cells or in specific populations within the immune or central nervous system (CNS) compartments, and induced experimental autoimmune encephalomyelitis (EAE), which models human Multiple Sclerosis (MS). This revealed that the CNS tissue-protective features of IL-12 are mediated by cells of the neuroectoderm, and not immune cells. Importantly, sections of brain from patients with MS show comparable patterns of expression, indicating parallel mechanisms in humans. By combining spectral flow cytometry, bulk and single-nucleus RNA sequencing, we uncovered an IL-12-induced neuroprotective adaption of the neuroectoderm critically involved in maintaining CNS tissue integrity during inflammation.
Published: 2022

7. Embryonic and neonatal waves generate distinct populations of hepatic ILC1s

Author: Colin Sparano, Darío Solís-Sayago, Anjali Vijaykumar, Chiara Rickenbach, Marijne Vermeer, Florian Ingelfinger, Gioana Litscher, André Fonseca, Caroline Mussak, Maud Mayoux, Christin Friedrich, César Nombela-Arrieta, Georg Gasteiger, Burkhard Becher, Sonia Tugues, University of Zurich, and Tugues, Sonia
Subjects: 2403 Immunology, Immunology, 610 Medicine & health, General Medicine, 10263 Institute of Experimental Immunology, Immunity, Innate, Killer Cells, Natural, Mice, Fetus, Liver, 10032 Clinic for Oncology and Hematology, 2723 Immunology and Allergy, Animals, 570 Life sciences, biology
Abstract: Group 1 innate lymphoid cells (ILCs) comprising circulating natural killer (cNK) cells and tissue-resident ILC1s are critical for host defense against pathogens and tumors. Despite a growing understanding of their role in homeostasis and disease, the ontogeny of group 1 ILCs remains largely unknown. Here, we used fate mapping and single-cell transcriptomics to comprehensively investigate the origin and turnover of murine group 1 ILCs. Whereas cNK cells are continuously replaced throughout life, we uncovered tissue-dependent development and turnover of ILC1s. A first wave of ILC1s emerges during embryogenesis in the liver and transiently colonizes fetal tissues. After birth, a second wave quickly replaces ILC1s in most tissues apart from the liver, where they layer with embryonic ILC1s, persist until adulthood, and undergo a specific developmental program. Whereas embryonically derived ILC1s give rise to a cytotoxic subset, the neonatal wave establishes the full spectrum of ILC1s. Our findings uncover key ontogenic features of murine group 1 ILCs and their association with cellular identities and functions.
Published: 2022

8. High-dimensional immune profiling identifies a biomarker to monitor dimethyl fumarate response in multiple sclerosis

Author: Martin Diebold, Edoardo Galli, Andreas Kopf, Nicholas S R Sanderson, Ilaria Callegari, Pascal Benkert, Nicolás Gonzalo Núñez, Florian Ingelfinger, Stefan Herms, Sven Cichon, Ludwig Kappos, Jens Kuhle, Burkhard Becher, Manfred Claassen, and Tobias Derfuss
Subjects: Interferon-gamma, Multiple Sclerosis, Multidisciplinary, Dimethyl Fumarate, Cytokines, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, ddc:500, T-Lymphocytes, Helper-Inducer, Single-Cell Analysis, Biomarkers, Pharmacological, Immunosuppressive Agents, Lymphocyte Depletion
Abstract: Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS). Despite its wide clinical use, the mechanisms underlying clinical response are not understood. This study aimed to reveal immune markers of therapeutic response to DMF treatment in MS. For this purpose, we prospectively collected peripheral blood mononuclear cells (PBMCs) from a highly characterized cohort of 44 individuals with MS before and at 12 and 48 wk of DMF treatment. Single cells were profiled using high-dimensional mass cytometry. To capture the heterogeneity of different immune subsets, we adopted a bioinformatic multipanel approach that allowed cell population–cluster assignment of more than 50 different parameters, including lineage and activation markers as well as chemokine receptors and cytokines. Data were further analyzed in a semiunbiased fashion implementing a supervised representation learning approach to capture subtle longitudinal immune changes characteristic for therapy response. With this approach, we identified a population of memory T helper cells expressing high levels of neuroinflammatory cytokines (granulocyte–macrophage colony-stimulating factor [GM-CSF], interferon γ [IFNγ]) as well as CXCR3, whose abundance correlated with treatment response. Using spectral flow cytometry, we confirmed these findings in a second cohort of patients. Serum neurofilament light-chain levels confirmed the correlation of this immune cell signature with axonal damage. The identified cell population is expanded in peripheral blood under natalizumab treatment, substantiating a specific role in treatment response. We propose that depletion of GM-CSF–, IFNγ-, and CXCR3-expressing T helper cells is the main mechanism of action of DMF and allows monitoring of treatment response., Proceedings of the National Academy of Sciences of the United States of America, 119 (31), ISSN:0027-8424, ISSN:1091-6490
Published: 2022

9. CAR T Cells and Their Immune Environment Synergize to Shape Distinct Immune Profiles in Response Versus Toxicity in B Cell Lymphoma Patients

Author: Stefanie Kreutmair, Maximilian M Schaefer, Sebastian Stolz, Carla Merten, Can Ulutekin, Florian Ingelfinger, Susanne Unger, Chiara Alberti, Tobias Wertheimer, Aakriti Sethi, Thorsten Zenz, Markus G Manz, Antonia Maria Susanne Müller, Corinne C Widmer, and Burkhard Becher
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022

10. Immunological Predictors of Dimethyl Fumarate-Induced Lymphopenia

Author: Martin Diebold, Edoardo Galli, Andreas Kopf, Nicholas Sanderson, Ilaria Callegari, Florian Ingelfinger, Nicolás Gonzalo Núñez, Pascal Benkert, Ludwig Kappos, Jens Kuhle, Burkhard Becher, Manfred Claassen, and Tobias Derfuss
Subjects: Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurology, Dimethyl Fumarate, Lymphopenia, Humans, Neurology (clinical), Prospective Studies, Immunosuppressive Agents
Abstract: Treatment with dimethyl fumarate (DMF) leads to lymphopenia and infectious complications in a subset of patients with multiple sclerosis (MS). Here, we aimed to reveal immune markers of DMF-associated lymphopenia. This prospective observational study longitudinally assessed 31 individuals with MS by single-cell mass cytometry before and after 12 and 48 weeks of DMF therapy. Employing a neural network-based representation learning approach, we identified a CCR4-expressing T helper cell population negatively associated with relevant lymphopenia. CCR4-expressing T helper cells represent a candidate prognostic biomarker for the development of relevant lymphopenia in patients undergoing DMF treatment. ANN NEUROL 2022;91:676-681.
Published: 2022

11. IFNγ and GM-CSF control complementary differentiation programs in the monocyte-to-phagocyte transition during neuroinflammation

Author: Ana Amorim, Donatella De Feo, Ekaterina Friebel, Florian Ingelfinger, Cyrill Dimitri Anderfuhren, Sinduya Krishnarajah, Myrto Andreadou, Christina A. Welsh, Zhaoyuan Liu, Florent Ginhoux, Melanie Greter, Burkhard Becher, University of Zurich, and Becher, Burkhard
Subjects: Male, Phagocytes, 2403 Immunology, Macrophages, Immunology, Granulocyte-Macrophage Colony-Stimulating Factor, Cell Differentiation, Mice, Transgenic, 610 Medicine & health, 10263 Institute of Experimental Immunology, Monocytes, Mice, Inbred C57BL, Interferon-gamma, Mice, Neuroinflammatory Diseases, 2723 Immunology and Allergy, Animals, Cytokines, Immunology and Allergy, 570 Life sciences, biology, Female
Abstract: During inflammation, Ly6C
Published: 2022

12. Pre-existing comorbidities shape the immune response associated with severe COVID-19

Author: Stefanie Kreutmair, Manuel Kauffmann, Susanne Unger, Florian Ingelfinger, Nicolás Gonzalo Núñez, Chiara Alberti, Donatella De Feo, Sinduya Krishnarajah, Ekaterina Friebel, Can Ulutekin, Sepideh Babaei, Benjamin Gaborit, Mirjam Lutz, Nicole Puertas Jurado, Nisar P. Malek, Siri Göpel, Peter Rosenberger, Helene A. Häberle, Ikram Ayoub, Sally Al-Hajj, Manfred Claassen, Roland Liblau, Guillaume Martin-Blondel, Michael Bitzer, Antoine Roquilly, and Burkhard Becher
Subjects: Metabolic Syndrome, SARS-CoV-2, Immunology, Immunity, Immunology and Allergy, COVID-19, Humans, Comorbidity, Renal Insufficiency, Chronic
Abstract: Comorbidities are risk factors for development of severe coronavirus disease 2019 (COVID-19). However, the extent to which an underlying comorbidity influences the immune response to severe acute respiratory syndrome coronavirus 2 remains unknown.Our aim was to investigate the complex interrelations of comorbidities, the immune response, and patient outcome in COVID-19.We used high-throughput, high-dimensional, single-cell mapping of peripheral blood leukocytes and algorithm-guided analysis.We discovered characteristic immune signatures associated not only with severe COVID-19 but also with the underlying medical condition. Different factors of the metabolic syndrome (obesity, hypertension, and diabetes) affected distinct immune populations, thereby additively increasing the immunodysregulatory effect when present in a single patient. Patients with disorders affecting the lung or heart, together with factors of metabolic syndrome, were clustered together, whereas immune disorder and chronic kidney disease displayed a distinct immune profile in COVID-19. In particular, severe acute respiratory syndrome coronavirus 2-infected patients with preexisting chronic kidney disease were characterized by the highest number of altered immune signatures of both lymphoid and myeloid immune branches. This overall major immune dysregulation could be the underlying mechanism for the estimated odds ratio of 16.3 for development of severe COVID-19 in this burdened cohort.The combinatorial systematic analysis of the immune signatures, comorbidities, and outcomes of patients with COVID-19 has provided the mechanistic immunologic underpinnings of comorbidity-driven patient risk and uncovered comorbidity-driven immune signatures.
Published: 2022
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13. Protection against autoimmunity is driven by thymic epithelial cell–mediated regulation of Tregdevelopment

Author: Ari Waisman, Pawel Durek, Nicole Puertas, Mir-Farzin Mashreghi, Marianne R. Spalinger, Stefan Floess, Mirjam Lutz, Ekaterina Friebel, Benedict Becher, Florian Ingelfinger, Florian Mair, Ana Amorim, Claudia Haftmann, Stefanie Schärli, Pascale Zwicky, Burkhard Becher, Jochen Huehn, René Riedel, Jan Kisielow, and Brian P. Leung
Subjects: medicine.anatomical_structure, T cell, Immunology, Thymic epithelial cell, medicine, Cancer research, General Medicine, Biology, medicine.disease_cause, Autoimmunity
Abstract: Medullary thymic epithelial cells (mTECs) are key antigen-presenting cells mediating T cell tolerance to prevent harmful autoimmunity. mTECs both negatively select self-reactive T cells and promote...
Published: 2021

14. Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of T

Author: Claudia, Haftmann, Pascale, Zwicky, Florian, Ingelfinger, Florian, Mair, Stefan, Floess, René, Riedel, Pawel, Durek, Marianne R, Spalinger, Ekaterina, Friebel, Brian P, Leung, Mirjam, Lutz, Nicole, Puertas, Ana, Amorim, Stefanie, Schärli, Benedict, Becher, Jan, Kisielow, Ari, Waisman, Mir-Farzin, Mashreghi, Jochen, Huehn, and Burkhard, Becher
Subjects: Mice, Inbred C57BL, Mice, Knockout, Mice, Mice, Congenic, Animals, Humans, Autoimmunity, Epithelial Cells, Forkhead Transcription Factors, Thymus Gland, Protein Serine-Threonine Kinases, T-Lymphocytes, Regulatory
Abstract: Medullary thymic epithelial cells (mTECs) are key antigen-presenting cells mediating T cell tolerance to prevent harmful autoimmunity. mTECs both negatively select self-reactive T cells and promote the development of thymic regulatory T cells (tT
Published: 2021

15. GM-CSF: Master regulator of the T cell-phagocyte interface during inflammation

Author: Donatella De Feo, Florian Ingelfinger, Burkhard Becher, and University of Zurich
Subjects: Phagocyte, T-Lymphocytes, Hematopoietic growth factor, T cell, Immunology, Inflammation, Context (language use), 610 Medicine & health, 10263 Institute of Experimental Immunology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Humans, Immunology and Allergy, Medicine, 030304 developmental biology, Phagocytes, 0303 health sciences, business.industry, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoiesis, Haematopoiesis, medicine.anatomical_structure, 570 Life sciences, biology, Myelopoiesis, medicine.symptom, business, 030215 immunology
Abstract: The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) was sequentially redefined during the past decades. Originally described as a hematopoietic growth factor for myelopoiesis, GM-CSF was recognized as a central mediator of inflammation bridging the innate and adaptive arms of the immune system. Phagocytes sensing GM-CSF adapt an inflammatory phenotype and facilitate pathogen clearance. However, in the context of chronic tissue inflammation, GM-CSF secreted by tissue-invading lymphocytes has detrimental effects by licensing tissue damage and hyperinflammation. Accordingly, therapeutic intervention at the T cell-phagocyte interface represents an attractive target to ameliorate disease progression and immunopathology. Although GM-CSF is largely dispensable for steady state myelopoiesis, dysregulation, as seen in chronic inflammatory diseases, may however lead to disrupted haematopoiesis and long-term effects on bone marrow output. Here, we will survey the role of GM-CSF during inflammation, discuss the extent to which GM-CSF-secreting T cells, debate their introduction as a separate T cell lineage and explore current and future clinical implications of GM-CSF in human disease settings.
Published: 2021

16. IL-12 regulates type 3 immunity through interfollicular keratinocytes in psoriasiform inflammation

Author: Salomé LeibundGut-Landmann, Mirjam Lutz, Stefanie Schärli, Christoph Schlapbach, Florian Ingelfinger, Truong San Phan, Bruno Marcel Silva de Melo, Fiorella Ruchti, Sarah Mundt, Julia-Tatjana Maul, Burkhard Becher, Nicole Puertas, Mitchell P. Levesque, Thomas M. Kündig, and Pascale Zwicky
Subjects: Keratinocytes, medicine.medical_treatment, Protein subunit, Immunology, Inflammation, Interleukin-23, Cell Line, Mice, Immunity, Psoriasis, medicine, Animals, Mice, Knockout, business.industry, Receptors, Interleukin-12, General Medicine, medicine.disease, Interleukin-12, Mice, Inbred C57BL, Cytokine, Dermatology clinic, Interleukin 12, medicine.symptom, business
Abstract: Psoriasis is a chronic inflammatory skin disorder underpinned by dysregulated cytokine signaling. Drugs neutralizing the common p40 subunit of interleukin-12 (IL-12) and IL-23 represented a therapeutic breakthrough; however, new drugs that block the IL-23p19 subunit and spare IL-12 are more effective, suggesting a regulatory function of IL-12. To pinpoint the cell type and underlying mechanism of IL-12–mediated immune regulation in psoriasis, we generated a conditional
Published: 2021

17. Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature

Author: Nicole Puertas Jurado, Edoardo Galli, David Bamert, Federica Sallusto, Sinduya Krishnarajah, Florian Ingelfinger, Hans H. Jung, Pascale Zwicky, Nicolás Gonzalo Núñez, Ayse Akarca, Sarah Mundt, Isabelle Opitz, Luca Piccoli, Donatella De Feo, Sebastian G. Utz, Didier Schneiter, Teresa Marafioti, Mirjam Lutz, Antonio Lanzavecchia, Michael Kramer, Burkhard Becher, Can Ulutekin, Bettina Schreiner, Corinne C Widmer, University of Zurich, Schreiner, Bettina, and Becher, Burkhard
Subjects: 0301 basic medicine, Male, 10255 Clinic for Thoracic Surgery, T-Lymphocytes, 2804 Cellular and Molecular Neuroscience, Autoimmunity, Tissue-resident T cells, Biomarker, Mass cytometry, Immunophenotyping, Thymus, Myasthenia gravis, Cytokines, medicine.disease_cause, Machine Learning, 0302 clinical medicine, Receptors, Cholinergic, Aged, 80 and over, B-Lymphocytes, Middle Aged, Thymectomy, 3. Good health, medicine.anatomical_structure, 2728 Neurology (clinical), Female, Single-Cell Analysis, Adult, T cell, 610 Medicine & health, Thymus Gland, Biology, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Immune system, Myasthenia Gravis, medicine, Humans, Aged, Autoantibodies, Autoimmune disease, Original Paper, Autoantibody, Correction, Immune dysregulation, medicine.disease, 10040 Clinic for Neurology, 2734 Pathology and Forensic Medicine, 030104 developmental biology, Immunology, 10032 Clinic for Oncology and Hematology, Neurology (clinical), Biomarkers, 030215 immunology
Abstract: Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG. By creating a comprehensive immune map, we identified two dysregulated subsets of inflammatory circulating memory T helper (Th) cells. These signature ThCD103 and ThGM cells populated the diseased thymus, were reduced in the blood of MG patients, and were inversely correlated with disease severity. Both signature Th subsets rebounded in the blood of MG patients after surgical thymus removal, indicative of their role as cellular markers of disease activity. Together, this in-depth analysis of the immune landscape of MG provides valuable insight into disease pathogenesis, suggests novel biomarkers and identifies new potential therapeutic targets for treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s00401-021-02299-y.
Published: 2021

18. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author: Lara Gibellini, Sussan Nourshargh, Susanna Cardell, Wlodzimierz Maslinski, Mar Felipo-Benavent, Florian Mair, Hans-Martin Jäck, Lilly Lopez, Klaus Warnatz, John Trowsdale, Diana Ordonez, Marcus Eich, William Hwang, Anne Cooke, Dirk Mielenz, Alberto Orfao, Winfried F. Pickl, Vladimir Benes, Alice Yue, T. Vincent Shankey, Maria Tsoumakidou, Virginia Litwin, Gelo Victoriano Dela Cruz, Andrea Cavani, Sara De Biasi, Larissa Nogueira Almeida, Jonathan J M Landry, Claudia Haftmann, Charlotte Esser, Ana Cumano, Anneke Wilharm, Francesco Dieli, Rudi Beyaert, Alessio Mazzoni, Burkhard Ludewig, Carlo Pucillo, Dirk H. Busch, Joe Trotter, Stipan Jonjić, Marc Veldhoen, Josef Spidlen, Aja M. Rieger, Dieter Adam, Srijit Khan, Todd A. Fehniger, Giuseppe Matarese, Maximilien Evrard, Christian Maueröder, Steffen Schmitt, Kristin A. Hogquist, Barry Moran, Raghavendra Palankar, Markus Feuerer, S Schmid, Susann Rahmig, Amy E. Lovett-Racke, James V. Watson, Megan K. Levings, Susanne Melzer, Dinko Pavlinic, Christopher M. Harpur, Christina Stehle, A. Graham Pockley, Toshinori Nakayama, Attila Tárnok, Juhao Yang, Michael Lohoff, Paulo Vieira, Francisco Sala-de-Oyanguren, Christian Kurts, Anastasia Gangaev, Alfonso Blanco, Hans Scherer, Regine J. Dress, Bruno Silva-Santos, Kiyoshi Takeda, Bimba F. Hoyer, Ilenia Cammarata, Daryl Grummitt, Isabel Panse, Günnur Deniz, Bianka Baying, Friederike Ebner, Esther Schimisky, Leo Hansmann, Thomas Kamradt, Edwin van der Pol, Daniel Scott-Algara, Anna Iannone, Giorgia Alvisi, Sebastian R. Schulz, Francesco Liotta, Irmgard Förster, Beatriz Jávega, Hans-Peter Rahn, Caetano Reis e Sousa, Livius Penter, Xuetao Cao, David P. Sester, Keisuke Goda, Peter Wurst, Iain B. McInnes, Ricardo T. Gazzinelli, Federica Piancone, Gerald Willimsky, Yotam Raz, Pärt Peterson, Wolfgang Fritzsche, Yvonne Samstag, Martin Büscher, Thomas Schüler, Susanne Hartmann, Robert J. Wilkinson, Anna E. S. Brooks, Steven L. C. Ketelaars, Catherine Sautès-Fridman, Anna Rubartelli, Petra Bacher, Katja Kobow, Marco A. Cassatella, Andrea Hauser, Henrik E. Mei, Kilian Schober, Silvia Della Bella, Graham Anderson, Michael D. Ward, Garth Cameron, Sebastian Lunemann, Katharina Kriegsmann, Katarzyna M. Sitnik, Brice Gaudilliere, Chantip Dang-Heine, Marcello Pinti, Paul Klenerman, Frank A. Schildberg, Joana Barros-Martins, Laura G. Rico, Hanlin Zhang, Christian Münz, Thomas Dörner, Jakob Zimmermann, Andrea M. Cooper, Jonni S. Moore, Andreas Diefenbach, Yanling Liu, Wolfgang Bauer, Tobit Steinmetz, Katharina Pracht, Leonard Tan, Peter K. Jani, Alan M. Stall, Petra Hoffmann, Christine S. Falk, Jasmin Knopf, Simon Fillatreau, Hans-Dieter Volk, Luis E. Muñoz, David L. Haviland, William W. Agace, Jonathan Rebhahn, Ljiljana Cvetkovic, Mohamed Trebak, Jordi Petriz, Mario Clerici, Diether J. Recktenwald, Anders Ståhlberg, Tristan Holland, Helen M. McGuire, Sa A. Wang, Christian Kukat, Thomas Kroneis, Laura Cook, Wan Ting Kong, Xin M. Wang, Britta Engelhardt, Pierre Coulie, Genny Del Zotto, Sally A. Quataert, Kata Filkor, Gabriele Multhoff, Bartek Rajwa, Federica Calzetti, Hans Minderman, Cosima T. Baldari, Jens Geginat, Hervé Luche, Gert Van Isterdael, Linda Schadt, Sophia Urbanczyk, Giovanna Borsellino, Liping Yu, Dale I. Godfrey, Achille Anselmo, Rachael C. Walker, Andreas Grützkau, David W. Hedley, Birgit Sawitzki, Silvia Piconese, Maria Yazdanbakhsh, Burkhard Becher, Ramon Bellmas Sanz, Michael Delacher, Hyun-Dong Chang, Immanuel Andrä, Hans-Gustaf Ljunggren, José-Enrique O'Connor, Ahad Khalilnezhad, Sharon Sanderson, Federico Colombo, Götz R. A. Ehrhardt, Inga Sandrock, Enrico Lugli, Christian Bogdan, James B. Wing, Susann Müller, Tomohiro Kurosaki, Derek Davies, Ester B. M. Remmerswaal, Kylie M. Quinn, Christopher A. Hunter, Andreas Radbruch, Timothy P. Bushnell, Anna Erdei, Sabine Adam-Klages, Pascale Eede, Van Duc Dang, Rieke Winkelmann, Thomas Korn, Gemma A. Foulds, Dirk Baumjohann, Matthias Schiemann, Manfred Kopf, Jan Kisielow, Lisa Richter, Jochen Huehn, Gloria Martrus, Alexander Scheffold, Jessica G. Borger, Sidonia B G Eckle, John Bellamy Foster, Anna Katharina Simon, Alicia Wong, Mübeccel Akdis, Gisa Tiegs, Toralf Kaiser, James McCluskey, Anna Vittoria Mattioli, Aaron J. Marshall, Hui-Fern Koay, Eva Orlowski-Oliver, Anja E. Hauser, J. Paul Robinson, Jay K. Kolls, Luca Battistini, Mairi McGrath, Jane L. Grogan, Natalio Garbi, Timothy Tree, Kingston H. G. Mills, Stefan H. E. Kaufmann, Wolfgang Schuh, Ryan R. Brinkman, Tim R. Mosmann, Vincenzo Barnaba, Andreas Dolf, Lorenzo Cosmi, Bo Huang, Andreia C. Lino, Baerbel Keller, René A. W. van Lier, Alexandra J. Corbett, Paul S. Frenette, Pleun Hombrink, Helena Radbruch, Sofie Van Gassen, Olivier Lantz, Lorenzo Moretta, Désirée Kunkel, Kirsten A. Ward-Hartstonge, Armin Saalmüller, Leslie Y. T. Leung, Salvador Vento-Asturias, Paola Lanuti, Alicia Martínez-Romero, Sarah Warth, Zhiyong Poon, Diana Dudziak, Andrea Cossarizza, Kovit Pattanapanyasat, Konrad von Volkmann, Jessica P. Houston, Agnès Lehuen, Andrew Filby, Pratip K. Chattopadhyay, Stefano Casola, Annika Wiedemann, Hannes Stockinger, Jürgen Ruland, Arturo Zychlinsky, Claudia Waskow, Katrin Neumann, Ari Waisman, Lucienne Chatenoud, Sudipto Bari, Kamran Ghoreschi, David W. Galbraith, Yvan Saeys, Hamida Hammad, Andrea Gori, Miguel López-Botet, Gabriel Núñez, Sabine Ivison, Michael Hundemer, Dorothea Reimer, Mark C. Dessing, Günter J. Hämmerling, Rudolf A. Manz, Tomas Kalina, Jonas Hahn, Holden T. Maecker, Hendy Kristyanto, Martin S. Davey, Henning Ulrich, Michael L. Dustin, Takashi Saito, Yousuke Takahama, Milena Nasi, Johanna Huber, Jürgen Wienands, Paolo Dellabona, Andreas Schlitzer, Michael D. Leipold, Kerstin H. Mair, Christian Peth, Immo Prinz, Chiara Romagnani, José M. González-Navajas, Josephine Schlosser, Marina Saresella, Matthias Edinger, Dirk Brenner, Nicole Baumgarth, Rikard Holmdahl, Fang-Ping Huang, Guadalupe Herrera, Malte Paulsen, Gergely Toldi, Luka Cicin-Sain, Reiner Schulte, Christina E. Zielinski, Thomas Winkler, Christoph Goettlinger, Philip E. Boulais, Jennie H M Yang, Antonio Celada, Heike Kunze-Schumacher, Julia Tornack, Florian Ingelfinger, Jenny Mjösberg, Andy Riddell, Leonie Wegener, Thomas Höfer, Christoph Hess, James P. Di Santo, Anna E. Oja, J. Kühne, Willem van de Veen, Mary Bebawy, Alberto Mantovani, Bart Everts, Giovanna Lombardi, Laura Maggi, Anouk von Borstel, Pia Kvistborg, Elisabetta Traggiai, A Ochel, Nima Aghaeepour, Charles-Antoine Dutertre, Matthieu Allez, Thomas Höllt, Wenjun Ouyang, Regina Stark, Maries van den Broek, Shimon Sakaguchi, Paul K. Wallace, Silvano Sozzani, Francesca LaRosa, Annette Oxenius, Malgorzata J. Podolska, Ivana Marventano, Wilhelm Gerner, Oliver F. Wirz, Britta Frehse, Gevitha Ravichandran, Martin Herrmann, Carl S. Goodyear, Gary Warnes, Helen Ferry, Stefan Frischbutter, Tim R. Radstake, Salomé LeibundGut-Landmann, Yi Zhao, Axel Schulz, Angela Santoni, Pablo Engel, Daniela C. Hernández, Andreas Acs, Cristiano Scottà, Francesco Annunziato, Thomas Weisenburger, Wolfgang Beisker, Sue Chow, Fritz Melchers, Daniel E. Speiser, Immanuel Kwok, Florent Ginhoux, Dominic A. Boardman, Natalie Stanley, Carsten Watzl, Marie Follo, Erik Lubberts, Andreas Krueger, Susanne Ziegler, Göran K. Hansson, David Voehringer, Antonia Niedobitek, Eleni Christakou, Lai Guan Ng, Sabine Baumgart, Nicholas A Gherardin, Antonio Cosma, Orla Maguire, Jolene Bradford, Daniel Schraivogel, Linda Quatrini, Stephen D. Miller, Rheumatology, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Internal Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-DENOTHE Center, Institute of Clinical Molecular Biology, Kiel University, Department of Life Sciences [Siena, Italy], Università degli Studi di Siena = University of Siena (UNISI), Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Dulbecco Telethon Institute/Department of Biology, Caprotec Bioanalytics GmbH, International Occultation Timing Association European Section (IOTA ES), International Occultation Timing Association European Section, European Molecular Biology Laboratory [Heidelberg] (EMBL), VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Fondazione Santa Lucia (IRCCS), Department of Immunology, Chinese Academy of Medical Sciences, FIRC Institute of Molecular Oncology Foundation, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physiopatology and Transplantation, University of Milan (DEPT), University of Milan, Monash University [Clayton], Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute of Cellular Pathology, Université Catholique de Louvain = Catholic University of Louvain (UCL), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Immunology Unit, Dept. of Oncology, DIBIT San Raffaele Scientific Institute, Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biopharmacy [Bruxelles, Belgium] (Institute for Medical Immunology IMI), Université libre de Bruxelles (ULB), Charité Hospital, Humboldt-Universität zu Berlin, Agency for science, technology and research [Singapore] (A*STAR), Laboratory of Molecular Immunology and the Howard Hughes Institute, Rockefeller University [New York], Kennedy Institute of Rheumatology [Oxford, UK], Imperial College London, Theodor Kocher Institute, University of Bern, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] ( IUF), Université Lumière - Lyon 2 (UL2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of Edinburgh, Integrative Biology Program [Milano], Istituto Nazionale Genetica Molecolare [Milano] (INGM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Universitat de Barcelona (UB), Rheumatologie, Cell Biology, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department for Internal Medicine 3, Institute for Clinical Immunology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Delft University of Technology (TU Delft), Medical Inflammation Research, Karolinska Institutet [Stockholm], Department of Photonics Engineering [Lyngby], Technical University of Denmark [Lyngby] (DTU), Dpt of Experimental Immunology [Braunschweig], Helmholtz Centre for Infection Research (HZI), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Department of Histology and Embryology, University of Rijeka, Freiburg University Medical Center, Nuffield Dept of Clinical Medicine, University of Oxford [Oxford]-NIHR Biomedical Research Centre, Institute of Integrative Biology, Molecular Biomedicine, Berlin Institute of Health (BIH), Laboratory for Lymphocyte Differentiation, RIKEN Research Center, Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Department of Surgery [Vancouver, BC, Canada] (Child and Family Research Institute), University of British Columbia (UBC)-Child and Family Research Institute [Vancouver, BC, Canada], College of Food Science and Technology [Shangai], Shanghai Ocean University, Institute for Medical Microbiology and Hygiene, University of Marburg, King‘s College London, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Brustzentrum Kantonsspital St. Gallen, Immunotechnology Section, Vaccine Research Center, National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Diseases, Heinrich Pette Institute [Hamburg], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Immunology and Cell Biology, Mario Negri Institute, Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi ONLUS Foundation, Institute of Translational Medicine, Klinik für Dermatologie, Venerologie und Allergologie, School of Biochemistry and Immunology, Department of Medicine Huddinge, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Lipid Laboratory, Università di Genova, Dipartimento di Medicina Sperimentale, Department of Environmental Microbiology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München (LMU), Centre de Recherche Publique- Santé, Université du Luxembourg (Uni.lu), William Harvey Research Institute, Barts and the London Medical School, University of Michigan [Ann Arbor], University of Michigan System, Centro de Investigacion del Cancer (CSIC), Universitario de Salamanca, Molecular Pathology [Tartu, Estonia], University of Tartu, Hannover Medical School [Hannover] (MHH), Centre d'Immunologie de Marseille - Luminy (CIML), Monash Biomedicine Discovery Institute, Cytometry Laboratories and School of Veterinary Medicine, Purdue University [West Lafayette], Data Mining and Modelling for Biomedicine [Ghent, Belgium], VIB Center for Inflammation Research [Ghent, Belgium], Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, RIKEN Research Center for Allergy and Immunology, Osaka University [Osaka], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institute of Medical Immunology [Berlin, Germany], FACS and Array Core Facility, Johannes Gutenberg - Universität Mainz (JGU), Otto-von-Guericke University [Magdeburg] (OVGU), SUPA School of Physics and Astronomy [University of St Andrews], University of St Andrews [Scotland]-Scottish Universities Physics Alliance (SUPA), Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), General Pathology and Immunology (GPI), University of Brescia, Université de Lausanne (UNIL), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Department of Molecular Immunology, Medizinische Universität Wien = Medical University of Vienna, Dept. Pediatric Cardiology, Universität Leipzig [Leipzig], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Cardiovascular Sciences, Albany Medical College, Dept Pathol, Div Immunol, University of Cambridge [UK] (CAM), Department of Information Technology [Gent], Universiteit Gent, Department of Plant Systems Biology, Department of Plant Biotechnology and Genetics, Universiteit Gent = Ghent University [Belgium] (UGENT), Division of Molecular Immunology, Institute for Immunology, Department of Geological Sciences, University of Oregon [Eugene], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, University of Colorado [Colorado Springs] (UCCS), FACS laboratory, Cancer Research, London, Cancer Research UK, Regeneration in Hematopoiesis and Animal Models of Hematopoiesis, Faculty of Medicine, Dresden University of Technology, Barbara Davis Center for Childhood Diabetes (BDC), University of Colorado Anschutz [Aurora], School of Computer and Electronic Information [Guangxi University], Guangxi University [Nanning], School of Materials Science and Engineering, Nanyang Technological University [Singapour], Max Planck Institute for Infection Biology (MPIIB), Max-Planck-Gesellschaft, Work in the laboratory of Dieter Adam is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Projektnummer 125440785 – SFB 877, Project B2.Petra Hoffmann, Andrea Hauser, and Matthias Edinger thank BD Biosciences®, San José, CA, USA, and SKAN AG, Bale, Switzerland for fruitful cooperation during the development, construction, and installation of the GMP‐compliant cell sorting equipment and the Bavarian Immune Therapy Network (BayImmuNet) for financial support.Edwin van der Pol and Paola Lanuti acknowledge Aleksandra Gąsecka M.D. for excellent experimental support and Dr. Rienk Nieuwland for textual suggestions. This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO‐TTW), research program VENI 15924.Jessica G Borger, Kylie M Quinn, Mairi McGrath, and Regina Stark thank Francesco Siracusa and Patrick Maschmeyer for providing data.Larissa Nogueira Almeida was supported by DFG research grant MA 2273/14‐1. Rudolf A. Manz was supported by the Excellence Cluster 'Inflammation at Interfaces' (EXC 306/2).Susanne Hartmann and Friederike Ebner were supported by the German Research Foundation (GRK 2046).Hans Minderman was supported by NIH R50CA211108.This work was funded by the Deutsche Forschungsgemeinschaft through the grant TRR130 (project P11 and C03) to Thomas H. Winkler.Ramon Bellmàs Sanz, Jenny Kühne, and Christine S. Falk thank Jana Keil and Kerstin Daemen for excellent technical support. The work was funded by the Germany Research Foundation CRC738/B3 (CSF).The work by the Mei laboratory was supported by German Research Foundation Grant ME 3644/5‐1 and TRR130 TP24, the German Rheumatism Research Centre Berlin, European Union Innovative Medicines Initiative ‐ Joint Undertaking ‐ RTCure Grant Agreement 777357, the Else Kröner‐Fresenius‐Foundation, German Federal Ministry of Education and Research e:Med sysINFLAME Program Grant 01ZX1306B and KMU‐innovativ 'InnoCyt', and the Leibniz Science Campus for Chronic Inflammation (http://www.chronische-entzuendung.org).Axel Ronald Schulz, Antonio Cosma, Sabine Baumgart, Brice Gaudilliere, Helen M. McGuire, and Henrik E. Mei thank Michael D. Leipold for critically reading the manuscript.Christian Kukat acknowledges support from the ISAC SRL Emerging Leaders program.John Trowsdale received funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant Agreement 695551)., European Project: 7728036(1978), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Firenze = University of Florence (UniFI)-DENOTHE Center, Università degli Studi di Milano = University of Milan (UNIMI), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] (IUF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universität Heidelberg [Heidelberg] = Heidelberg University, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), University of Oxford-NIHR Biomedical Research Centre, Universität Bonn = University of Bonn, Università degli Studi di Firenze = University of Florence (UniFI), Università degli studi di Genova = University of Genoa (UniGe), Universidad de Salamanca, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Université de Lausanne = University of Lausanne (UNIL), Universität Leipzig, Universiteit Gent = Ghent University (UGENT), HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., Cossarizza, A., Chang, H. -D., Radbruch, A., Acs, A., Adam, D., Adam-Klages, S., Agace, W. W., Aghaeepour, N., Akdis, M., Allez, M., Almeida, L. N., Alvisi, G., Anderson, G., Andra, I., Annunziato, F., Anselmo, A., Bacher, P., Baldari, C. T., Bari, S., Barnaba, V., Barros-Martins, J., Battistini, L., Bauer, W., Baumgart, S., Baumgarth, N., Baumjohann, D., Baying, B., Bebawy, M., Becher, B., Beisker, W., Benes, V., Beyaert, R., Blanco, A., Boardman, D. A., Bogdan, C., Borger, J. G., Borsellino, G., Boulais, P. E., Bradford, J. A., Brenner, D., Brinkman, R. R., Brooks, A. E. S., Busch, D. H., Buscher, M., Bushnell, T. P., Calzetti, F., Cameron, G., Cammarata, I., Cao, X., Cardell, S. L., Casola, S., Cassatella, M. A., Cavani, A., Celada, A., Chatenoud, L., Chattopadhyay, P. K., Chow, S., Christakou, E., Cicin-Sain, L., Clerici, M., Colombo, F. S., Cook, L., Cooke, A., Cooper, A. M., Corbett, A. J., Cosma, A., Cosmi, L., Coulie, P. G., Cumano, A., Cvetkovic, L., Dang, V. D., Dang-Heine, C., Davey, M. S., Davies, D., De Biasi, S., Del Zotto, G., Dela Cruz, G. V., Delacher, M., Della Bella, S., Dellabona, P., Deniz, G., Dessing, M., Di Santo, J. P., Diefenbach, A., Dieli, F., Dolf, A., Dorner, T., Dress, R. J., Dudziak, D., Dustin, M., Dutertre, C. -A., Ebner, F., Eckle, S. B. G., Edinger, M., Eede, P., Ehrhardt, G. R. A., Eich, M., Engel, P., Engelhardt, B., Erdei, A., Esser, C., Everts, B., Evrard, M., Falk, C. S., Fehniger, T. A., Felipo-Benavent, M., Ferry, H., Feuerer, M., Filby, A., Filkor, K., Fillatreau, S., Follo, M., Forster, I., Foster, J., Foulds, G. A., Frehse, B., Frenette, P. S., Frischbutter, S., Fritzsche, W., Galbraith, D. W., Gangaev, A., Garbi, N., Gaudilliere, B., Gazzinelli, R. T., Geginat, J., Gerner, W., Gherardin, N. A., Ghoreschi, K., Gibellini, L., Ginhoux, F., Goda, K., Godfrey, D. I., Goettlinger, C., Gonzalez-Navajas, J. M., Goodyear, C. S., Gori, A., Grogan, J. L., Grummitt, D., Grutzkau, A., Haftmann, C., Hahn, J., Hammad, H., Hammerling, G., Hansmann, L., Hansson, G., Harpur, C. M., Hartmann, S., Hauser, A., Hauser, A. E., Haviland, D. L., Hedley, D., Hernandez, D. C., Herrera, G., Herrmann, M., Hess, C., Hofer, T., Hoffmann, P., Hogquist, K., Holland, T., Hollt, T., Holmdahl, R., Hombrink, P., Houston, J. P., Hoyer, B. F., Huang, B., Huang, F. -P., Huber, J. E., Huehn, J., Hundemer, M., Hunter, C. A., Hwang, W. Y. K., Iannone, A., Ingelfinger, F., Ivison, S. M., Jack, H. -M., Jani, P. K., Javega, B., Jonjic, S., Kaiser, T., Kalina, T., Kamradt, T., Kaufmann, S. H. E., Keller, B., Ketelaars, S. L. C., Khalilnezhad, A., Khan, S., Kisielow, J., Klenerman, P., Knopf, J., Koay, H. -F., Kobow, K., Kolls, J. K., Kong, W. T., Kopf, M., Korn, T., Kriegsmann, K., Kristyanto, H., Kroneis, T., Krueger, A., Kuhne, J., Kukat, C., Kunkel, D., Kunze-Schumacher, H., Kurosaki, T., Kurts, C., Kvistborg, P., Kwok, I., Landry, J., Lantz, O., Lanuti, P., Larosa, F., Lehuen, A., LeibundGut-Landmann, S., Leipold, M. D., Leung, L. Y. T., Levings, M. K., Lino, A. C., Liotta, F., Litwin, V., Liu, Y., Ljunggren, H. -G., Lohoff, M., Lombardi, G., Lopez, L., Lopez-Botet, M., Lovett-Racke, A. E., Lubberts, E., Luche, H., Ludewig, B., Lugli, E., Lunemann, S., Maecker, H. T., Maggi, L., Maguire, O., Mair, F., Mair, K. H., Mantovani, A., Manz, R. A., Marshall, A. J., Martinez-Romero, A., Martrus, G., Marventano, I., Maslinski, W., Matarese, G., Mattioli, A. V., Maueroder, C., Mazzoni, A., Mccluskey, J., Mcgrath, M., Mcguire, H. M., Mcinnes, I. B., Mei, H. E., Melchers, F., Melzer, S., Mielenz, D., Miller, S. D., Mills, K. H. G., Minderman, H., Mjosberg, J., Moore, J., Moran, B., Moretta, L., Mosmann, T. R., Muller, S., Multhoff, G., Munoz, L. E., Munz, C., Nakayama, T., Nasi, M., Neumann, K., Ng, L. G., Niedobitek, A., Nourshargh, S., Nunez, G., O'Connor, J. -E., Ochel, A., Oja, A., Ordonez, D., Orfao, A., Orlowski-Oliver, E., Ouyang, W., Oxenius, A., Palankar, R., Panse, I., Pattanapanyasat, K., Paulsen, M., Pavlinic, D., Penter, L., Peterson, P., Peth, C., Petriz, J., Piancone, F., Pickl, W. F., Piconese, S., Pinti, M., Pockley, A. G., Podolska, M. J., Poon, Z., Pracht, K., Prinz, I., Pucillo, C. E. M., Quataert, S. A., Quatrini, L., Quinn, K. M., Radbruch, H., Radstake, T. R. D. J., Rahmig, S., Rahn, H. -P., Rajwa, B., Ravichandran, G., Raz, Y., Rebhahn, J. A., Recktenwald, D., Reimer, D., Reis e Sousa, C., Remmerswaal, E. B. M., Richter, L., Rico, L. G., Riddell, A., Rieger, A. M., Robinson, J. P., Romagnani, C., Rubartelli, A., Ruland, J., Saalmuller, A., Saeys, Y., Saito, T., Sakaguchi, S., Sala-de-Oyanguren, F., Samstag, Y., Sanderson, S., Sandrock, I., Santoni, A., Sanz, R. B., Saresella, M., Sautes-Fridman, C., Sawitzki, B., Schadt, L., Scheffold, A., Scherer, H. U., Schiemann, M., Schildberg, F. A., Schimisky, E., Schlitzer, A., Schlosser, J., Schmid, S., Schmitt, S., Schober, K., Schraivogel, D., Schuh, W., Schuler, T., Schulte, R., Schulz, A. R., Schulz, S. R., Scotta, C., Scott-Algara, D., Sester, D. P., Shankey, T. V., Silva-Santos, B., Simon, A. K., Sitnik, K. M., Sozzani, S., Speiser, D. E., Spidlen, J., Stahlberg, A., Stall, A. M., Stanley, N., Stark, R., Stehle, C., Steinmetz, T., Stockinger, H., Takahama, Y., Takeda, K., Tan, L., Tarnok, A., Tiegs, G., Toldi, G., Tornack, J., Traggiai, E., Trebak, M., Tree, T. I. M., Trotter, J., Trowsdale, J., Tsoumakidou, M., Ulrich, H., Urbanczyk, S., van de Veen, W., van den Broek, M., van der Pol, E., Van Gassen, S., Van Isterdael, G., van Lier, R. A. W., Veldhoen, M., Vento-Asturias, S., Vieira, P., Voehringer, D., Volk, H. -D., von Borstel, A., von Volkmann, K., Waisman, A., Walker, R. V., Wallace, P. K., Wang, S. A., Wang, X. M., Ward, M. D., Ward-Hartstonge, K. A., Warnatz, K., Warnes, G., Warth, S., Waskow, C., Watson, J. V., Watzl, C., Wegener, L., Weisenburger, T., Wiedemann, A., Wienands, J., Wilharm, A., Wilkinson, R. J., Willimsky, G., Wing, J. B., Winkelmann, R., Winkler, T. H., Wirz, O. F., Wong, A., Wurst, P., Yang, J. H. M., Yang, J., Yazdanbakhsh, M., Yu, L., Yue, A., Zhang, H., Zhao, Y., Ziegler, S. M., Zielinski, C., Zimmermann, J., Zychlinsky, A., UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/GECE - Génétique cellulaire, Netherlands Organization for Scientific Research, German Research Foundation, European Commission, European Research Council, Repositório da Universidade de Lisboa, CCA - Imaging and biomarkers, Experimental Immunology, AII - Infectious diseases, AII - Inflammatory diseases, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, and Landsteiner Laboratory
Subjects: 0301 basic medicine, Consensus, Immunology, Consensu, Cell Separation, Biology, Article, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Guidelines, Allergy and Immunology, medicine, Cell separation, Immunology and Allergy, Humans, guidelines, flow cytometry, immunology, medicine.diagnostic_test, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Cell sorting, Flow Cytometry, Cell selection, Data science, 3. Good health, 030104 developmental biology, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, 030215 immunology, Human
Abstract: All authors: Andrea Cossarizza Hyun‐Dong Chang Andreas Radbruch Andreas Acs Dieter Adam Sabine Adam‐Klages William W. Agace Nima Aghaeepour Mübeccel Akdis Matthieu Allez Larissa Nogueira Almeida Giorgia Alvisi Graham Anderson Immanuel Andrä Francesco Annunziato Achille Anselmo Petra Bacher Cosima T. Baldari Sudipto Bari Vincenzo Barnaba Joana Barros‐Martins Luca Battistini Wolfgang Bauer Sabine Baumgart Nicole Baumgarth Dirk Baumjohann Bianka Baying Mary Bebawy Burkhard Becher Wolfgang Beisker Vladimir Benes Rudi Beyaert Alfonso Blanco Dominic A. Boardman Christian Bogdan Jessica G. Borger Giovanna Borsellino Philip E. Boulais Jolene A. Bradford Dirk Brenner Ryan R. Brinkman Anna E. S. Brooks Dirk H. Busch Martin Büscher Timothy P. Bushnell Federica Calzetti Garth Cameron Ilenia Cammarata Xuetao Cao Susanna L. Cardell Stefano Casola Marco A. Cassatella Andrea Cavani Antonio Celada Lucienne Chatenoud Pratip K. Chattopadhyay Sue Chow Eleni Christakou Luka Čičin‐Šain Mario Clerici Federico S. Colombo Laura Cook Anne Cooke Andrea M. Cooper Alexandra J. Corbett Antonio Cosma Lorenzo Cosmi Pierre G. Coulie Ana Cumano Ljiljana Cvetkovic Van Duc Dang Chantip Dang‐Heine Martin S. Davey Derek Davies Sara De Biasi Genny Del Zotto Gelo Victoriano Dela Cruz Michael Delacher Silvia Della Bella Paolo Dellabona Günnur Deniz Mark Dessing James P. Di Santo Andreas Diefenbach Francesco Dieli Andreas Dolf Thomas Dörner Regine J. Dress Diana Dudziak Michael Dustin Charles‐Antoine Dutertre Friederike Ebner Sidonia B. G. Eckle Matthias Edinger Pascale Eede Götz R.A. Ehrhardt Marcus Eich Pablo Engel Britta Engelhardt Anna Erdei Charlotte Esser Bart Everts Maximilien Evrard Christine S. Falk Todd A. Fehniger Mar Felipo‐Benavent Helen Ferry Markus Feuerer Andrew Filby Kata Filkor Simon Fillatreau Marie Follo Irmgard Förster John Foster Gemma A. Foulds Britta Frehse Paul S. Frenette Stefan Frischbutter Wolfgang Fritzsche David W. Galbraith Anastasia Gangaev Natalio Garbi Brice Gaudilliere Ricardo T. Gazzinelli Jens Geginat Wilhelm Gerner Nicholas A. Gherardin Kamran Ghoreschi Lara Gibellini Florent Ginhoux Keisuke Goda Dale I. Godfrey Christoph Goettlinger Jose M. González‐Navajas Carl S. Goodyear Andrea Gori Jane L. Grogan Daryl Grummitt Andreas Grützkau Claudia Haftmann Jonas Hahn Hamida Hammad Günter Hämmerling Leo Hansmann Goran Hansson Christopher M. Harpur Susanne Hartmann Andrea Hauser Anja E. Hauser David L. Haviland David Hedley Daniela C. Hernández Guadalupe Herrera Martin Herrmann Christoph Hess Thomas Höfer Petra Hoffmann Kristin Hogquist Tristan Holland Thomas Höllt Rikard Holmdahl Pleun Hombrink Jessica P. Houston Bimba F. Hoyer Bo Huang Fang‐Ping Huang Johanna E. Huber Jochen Huehn Michael Hundemer Christopher A. Hunter William Y. K. Hwang Anna Iannone Florian Ingelfinger Sabine M Ivison Hans‐Martin Jäck Peter K. Jani Beatriz Jávega Stipan Jonjic Toralf Kaiser Tomas Kalina Thomas Kamradt Stefan H. E. Kaufmann Baerbel Keller Steven L. C. Ketelaars Ahad Khalilnezhad Srijit Khan Jan Kisielow Paul Klenerman Jasmin Knopf Hui‐Fern Koay Katja Kobow Jay K. Kolls Wan Ting Kong Manfred Kopf Thomas Korn Katharina Kriegsmann Hendy Kristyanto Thomas Kroneis Andreas Krueger Jenny Kühne Christian Kukat Désirée Kunkel Heike Kunze‐Schumacher Tomohiro Kurosaki Christian Kurts Pia Kvistborg Immanuel Kwok Jonathan Landry Olivier Lantz Paola Lanuti Francesca LaRosa Agnès Lehuen Salomé LeibundGut‐Landmann Michael D. Leipold Leslie Y.T. Leung Megan K. Levings Andreia C. Lino Francesco Liotta Virginia Litwin Yanling Liu Hans‐Gustaf Ljunggren Michael Lohoff Giovanna Lombardi Lilly Lopez Miguel López‐Botet Amy E. Lovett‐Racke Erik Lubberts Herve Luche Burkhard Ludewig Enrico Lugli Sebastian Lunemann Holden T. Maecker Laura Maggi Orla Maguire Florian Mair Kerstin H. Mair Alberto Mantovani Rudolf A. Manz Aaron J. Marshall Alicia Martínez‐Romero Glòria Martrus Ivana Marventano Wlodzimierz Maslinski Giuseppe Matarese Anna Vittoria Mattioli Christian Maueröder Alessio Mazzoni James McCluskey Mairi McGrath Helen M. McGuire Iain B. McInnes Henrik E. Mei Fritz Melchers Susanne Melzer Dirk Mielenz Stephen D. Miller Kingston H.G. Mills Hans Minderman Jenny Mjösberg Jonni Moore Barry Moran Lorenzo Moretta Tim R. Mosmann Susann Müller Gabriele Multhoff Luis Enrique Muñoz Christian Münz Toshinori Nakayama Milena Nasi Katrin Neumann Lai Guan Ng Antonia Niedobitek Sussan Nourshargh Gabriel Núñez José‐Enrique O'Connor Aaron Ochel Anna Oja Diana Ordonez Alberto Orfao Eva Orlowski‐Oliver Wenjun Ouyang Annette Oxenius Raghavendra Palankar Isabel Panse Kovit Pattanapanyasat Malte Paulsen Dinko Pavlinic Livius Penter Pärt Peterson Christian Peth Jordi Petriz Federica Piancone Winfried F. Pickl Silvia Piconese Marcello Pinti A. Graham Pockley Malgorzata Justyna Podolska Zhiyong Poon Katharina Pracht Immo Prinz Carlo E. M. Pucillo Sally A. Quataert Linda Quatrini Kylie M. Quinn Helena Radbruch Tim R. D. J. Radstake Susann Rahmig Hans‐Peter Rahn Bartek Rajwa Gevitha Ravichandran Yotam Raz Jonathan A. Rebhahn Diether Recktenwald Dorothea Reimer Caetano Reis e Sousa Ester B.M. Remmerswaal Lisa Richter Laura G. Rico Andy Riddell Aja M. Rieger J. Paul Robinson Chiara Romagnani Anna Rubartelli Jürgen Ruland Armin Saalmüller Yvan Saeys Takashi Saito Shimon Sakaguchi Francisco Sala‐de‐Oyanguren Yvonne Samstag Sharon Sanderson Inga Sandrock Angela Santoni Ramon Bellmàs Sanz Marina Saresella Catherine Sautes‐Fridman Birgit Sawitzki Linda Schadt Alexander Scheffold Hans U. Scherer Matthias Schiemann Frank A. Schildberg Esther Schimisky Andreas Schlitzer Josephine Schlosser Stephan Schmid Steffen Schmitt Kilian Schober Daniel Schraivogel Wolfgang Schuh Thomas Schüler Reiner Schulte Axel Ronald Schulz Sebastian R. Schulz Cristiano Scottá Daniel Scott‐Algara David P. Sester T. Vincent Shankey Bruno Silva‐Santos Anna Katharina Simon Katarzyna M. Sitnik Silvano Sozzani Daniel E. Speiser Josef Spidlen Anders Stahlberg Alan M. Stall Natalie Stanley Regina Stark Christina Stehle Tobit Steinmetz Hannes Stockinger Yousuke Takahama Kiyoshi Takeda Leonard Tan Attila Tárnok Gisa Tiegs Gergely Toldi Julia Tornack Elisabetta Traggiai Mohamed Trebak Timothy I.M. Tree Joe Trotter John Trowsdale Maria Tsoumakidou Henning Ulrich Sophia Urbanczyk Willem van de Veen Maries van den Broek Edwin van der Pol Sofie Van Gassen Gert Van Isterdael René A.W. van Lier Marc Veldhoen Salvador Vento‐Asturias Paulo Vieira David Voehringer Hans‐Dieter Volk Anouk von Borstel Konrad von Volkmann Ari Waisman Rachael V. Walker Paul K. Wallace Sa A. Wang Xin M. Wang Michael D. Ward Kirsten A Ward‐Hartstonge Klaus Warnatz Gary Warnes Sarah Warth Claudia Waskow James V. Watson Carsten Watzl Leonie Wegener Thomas Weisenburger Annika Wiedemann Jürgen Wienands Anneke Wilharm Robert John Wilkinson Gerald Willimsky James B. Wing Rieke Winkelmann Thomas H. Winkler Oliver F. Wirz Alicia Wong Peter Wurst Jennie H. M. Yang Juhao Yang Maria Yazdanbakhsh Liping Yu Alice Yue Hanlin Zhang Yi Zhao Susanne Maria Ziegler Christina Zielinski Jakob Zimmermann Arturo Zychlinsky., These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion., This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO-TTW), research program VENI 15924. This work was funded by the Deutsche Forschungsgemeinschaft. European Union Innovative Medicines Initiative - Joint Undertaking - RTCure Grant Agreement 777357 and innovation program (Grant Agreement 695551).
Published: 2019

19. Single-cell multiomics in neuroinflammation

Author: Florian Ingelfinger, Eduardo Beltrán, Lisa A Gerdes, and Burkhard Becher
Subjects: Central Nervous System, Inflammation, Neuroinflammatory Diseases, Immunology, Humans, Immunology and Allergy
Abstract: The central nervous system (CNS) is, more than other organs, particularly vulnerable to inflammation and immune responses must be tightly controlled in order to maintain host protection. Accordingly, neuroinflammation is an orchestrated process involving various cell types that may dramatically change their phenotypic and functional properties upon entering the CNS. Recent advances in single-cell multiomics offer the unique opportunity to resolve this cellular heterogeneity in a holistic fashion and reshape our understanding of the molecular and cellular processes during neuroinflammation. Here, we provide an overview of technical advances in single-cell multiomics and the tremendous impact on our basic understanding of neuroinflammation. We discuss insights obtained in neuroinflammatory diseases and elaborate to which extent these tool sets could be applied in a clinical setting.
Published: 2022

20. Twin study reveals non-heritable immune perturbations in multiple sclerosis

Author: Florian Ingelfinger, Lisa Ann Gerdes, Vladyslav Kavaka, Sinduya Krishnarajah, Ekaterina Friebel, Edoardo Galli, Pascale Zwicky, Reinhard Furrer, Christian Peukert, Charles-Antoine Dutertre, Klara Magdalena Eglseer, Florent Ginhoux, Andrea Flierl-Hecht, Tania Kümpfel, Donatella De Feo, Bettina Schreiner, Sarah Mundt, Martin Kerschensteiner, Reinhard Hohlfeld, Eduardo Beltrán, Burkhard Becher, University of Zurich, and Becher, Burkhard
Subjects: 1000 Multidisciplinary, Multidisciplinary, Multiple Sclerosis, 610 Medicine & health, OX40 Ligand, Twins, Monozygotic, 10263 Institute of Experimental Immunology, 10040 Clinic for Neurology, 10123 Institute of Mathematics, 510 Mathematics, 10231 Institute for Computational Science, Twins, Dizygotic, 570 Life sciences, biology, Humans, Interleukin-2, Genetic Predisposition to Disease
Abstract: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system underpinned by partially understood genetic risk factors and environmental triggers and their undefined interactions1,2. Here we investigated the peripheral immune signatures of 61 monozygotic twin pairs discordant for MS to dissect the influence of genetic predisposition and environmental factors. Using complementary multimodal high-throughput and high-dimensional single-cell technologies in conjunction with data-driven computational tools, we identified an inflammatory shift in a monocyte cluster of twins with MS, coupled with the emergence of a population of IL-2 hyper-responsive transitional naive helper T cells as MS-related immune alterations. By integrating data on the immune profiles of healthy monozygotic and dizygotic twin pairs, we estimated the variance in CD25 expression by helper T cells displaying a naive phenotype to be largely driven by genetic and shared early environmental influences. Nonetheless, the expanding helper T cells of twins with MS, which were also elevated in non-twin patients with MS, emerged independent of the individual genetic makeup. These cells expressed central nervous system-homing receptors, exhibited a dysregulated CD25–IL-2 axis, and their proliferative capacity positively correlated with MS severity. Together, our matched-pair analysis of the extended twin approach allowed us to discern genetically and environmentally determined features of an MS-associated immune signature.
Published: 2021

21. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

Author: Mirjam Lutz, Ekaterina Friebel, Roland S. Liblau, Antoine Roquilly, Guillaume Martin-Blondel, Manfred Claassen, Benjamin Gaborit, Manuel Kauffmann, Sepideh Babaei, Donatella De Feo, Nicolás Gonzalo Núñez, Nisar P. Malek, Chiara Alberti, Sally Al-Hajj, Susanne Unger, Siri Goepel, Ikram Ayoub, Helene A. Häberle, Jakob Nilsson, Nicole Puertas Jurado, Peter Rosenberger, Stefanie Kreutmair, Sinduya Krishnarajah, Burkhard Becher, Michael Bitzer, Florian Ingelfinger, Pistre, Karine, Universität Zürich [Zürich] = University of Zurich (UZH), German Cancer Consortium [Heidelberg] (DKTK), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institute of Experimental Immunology [Zurich], Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), German Center for Infectious Research - partner site Tübingen [Tübingen, Allemagne] (DZIF), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University hospital of Zurich [Zurich], University of Zurich, and Becher, Burkhard
Subjects: 0301 basic medicine, CD4-Positive T-Lymphocytes, Male, MESH: CD4-Positive T-Lymphocytes / immunology, MESH: Biomarkers / blood, [SDV]Life Sciences [q-bio], MESH: HLA Antigens / genetics, MESH: COVID-19 / pathology, 10263 Institute of Experimental Immunology, Hospital-acquired pneumonia, Severity of Illness Index, 0302 clinical medicine, MESH: Pneumonia / immunology, HLA Antigens, T-Lymphocyte Subsets, peptide binding strength, Immunopathology, Immunology and Allergy, MESH: Pneumonia / pathology, MESH: T-Lymphocyte Subsets / metabolism, COVID, high-dimensional single cell analysis, Antigen Presentation, MESH: Middle Aged, spectral flow cytometry, immune profiling, MESH: SARS-CoV-2 / immunology, Middle Aged, Acquired immune system, MESH: HLA Antigens / immunology, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, HLA typing, 030220 oncology & carcinogenesis, MESH: T-Lymphocyte Subsets / immunology, 2723 Immunology and Allergy, MESH: SARS-CoV-2 / pathogenicity, Biomarker (medicine), Cytokines, biomarker, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Immunity, Innate, Angiotensin-Converting Enzyme 2, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Immunophenotyping, Immunology, Antigen presentation, 610 Medicine & health, Human leukocyte antigen, Biology, Article, 03 medical and health sciences, MESH: Natural Killer T-Cells / immunology, Immune system, immunophenotyping, MESH: CD4-Positive T-Lymphocytes / metabolism, MESH: Angiotensin-Converting Enzyme 2 / metabolism, MESH: Severity of Illness Index, medicine, Humans, 2403 Immunology, SARS-CoV-2, COVID-19, GM-CSF, 2725 Infectious Diseases, Pneumonia, biochemical phenomena, metabolism, and nutrition, medicine.disease, MESH: COVID-19 / immunology, Immunity, Innate, 030104 developmental biology, MESH: Antigen Presentation, 10033 Clinic for Immunology, 570 Life sciences, biology, Natural Killer T-Cells, Biomarkers
Abstract: Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2-petides to the patients’ HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Towards clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19., Graphical Abstract, The pathogen-specific immune alterations in severe COVID-19 remain unknown. Using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided comparison of COVID-19 vs. non-SARS-CoV-2-pneumonia patient samples, Kreutmair et al. identify T and NK cell immune signatures specific to SARS-CoV-2. They furthermore reveal NKT cell frequency as a predictive biomarker for COVID-19 outcome prediction and link impaired virus recognition to HLA genetics.
Published: 2021

22. Correction to: Single‑cell profiling of myasthenia gravis identifies a pathogenic T cell signature

Author: Sinduya Krishnarajah, Luca Piccoli, Corinne C Widmer, Sarah Mundt, Pascale Zwicky, Didier Schneiter, Edoardo Galli, Nicole Puertas Jurado, Donatella De Feo, Can Ulutekin, Burkhard Becher, Ayse Akarca, Bettina Schreiner, Sebastian G. Utz, Nicolás Gonzalo Núñez, Teresa Marafioti, Antonio Lanzavecchia, Mirjam Lutz, David Bamert, Hans H. Jung, Isabelle Opitz, Federica Sallusto, Florian Ingelfinger, and Michael Kramer
Subjects: Autoimmune disease, T cell, Autoantibody, Immune dysregulation, Biology, medicine.disease, medicine.disease_cause, Myasthenia gravis, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, medicine.anatomical_structure, Immune system, Immunology, medicine, Neurology (clinical), Cytometry, Acetylcholine receptor
Abstract: Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG. By creating a comprehensive immune map, we identified two dysregulated subsets of inflammatory circulating memory T helper (Th) cells. These signature ThCD103 and ThGM cells populated the diseased thymus, were reduced in the blood of MG patients, and were inversely correlated with disease severity. Both signature Th subsets rebounded in the blood of MG patients after surgical thymus removal, indicative of their role as cellular markers of disease activity. Together, this in-depth analysis of the immune landscape of MG provides valuable insight into disease pathogenesis, suggests novel biomarkers and identifies new potential therapeutic targets for treatment.
Published: 2021

23. GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis

Author: Manfred Claassen, Nicholas S. R. Sanderson, Eirini Arvaniti, Felix J. Hartmann, Martin Diebold, Burkhard Becher, Mohsen Khademi, Fredrik Piehl, Dunja Mrdjen, Tobias Derfuss, Edoardo Galli, Tomas Olsson, Christine Stadelmann, Faiez Al Nimer, Carsten Krieg, Bettina Schreiner, Franziska van der Meer, Florian Ingelfinger, University of Zurich, and Becher, Burkhard
Subjects: 0301 basic medicine, Receptors, CXCR4, Multiple Sclerosis, medicine.medical_treatment, T cell, Population, 610 Medicine & health, 10263 Institute of Experimental Immunology, CXCR4, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Chemokine receptor, 0302 clinical medicine, 1300 General Biochemistry, Genetics and Molecular Biology, Medicine, Humans, Mass cytometry, education, education.field_of_study, business.industry, Multiple sclerosis, Granulocyte-Macrophage Colony-Stimulating Factor, General Medicine, T helper cell, T-Lymphocytes, Helper-Inducer, medicine.disease, 10040 Clinic for Neurology, 030104 developmental biology, medicine.anatomical_structure, Cytokine, 030220 oncology & carcinogenesis, Immunology, 570 Life sciences, biology, Cytokines, business, Immunologic Memory, Algorithms, Signal Transduction
Abstract: Cytokine dysregulation is a central driver of chronic inflammatory diseases such as multiple sclerosis (MS). Here, we sought to determine the characteristic cellular and cytokine polarization profile in patients with relapsing-remitting multiple sclerosis (RRMS) by high-dimensional single-cell mass cytometry (CyTOF). Using a combination of neural network-based representation learning algorithms, we identified an expanded T helper cell subset in patients with MS, characterized by the expression of granulocyte-macrophage colony-stimulating factor and the C-X-C chemokine receptor type 4. This cellular signature, which includes expression of very late antigen 4 in peripheral blood, was also enriched in the central nervous system of patients with relapsing-remitting multiple sclerosis. In independent validation cohorts, we confirmed that this cell population is increased in patients with MS compared with other inflammatory and non-inflammatory conditions. Lastly, we also found the population to be reduced under effective disease-modifying therapy, suggesting that the identified T cell profile represents a specific therapeutic target in MS.
Published: 2019

24. Myasthenia gravis: From single cell signatures to cancer diagnosis

Author: Florian Ingelfinger, Michael Kramer, Sebastian Utz, Sarah Mundt, Sinduya Krishnarajah, Edoardo Galli, Mirjam Lutz, Nicole Puertas Jurado, Corinne Widmer, Ina Camille Reichen, Luca Piccoli, Federica Sallusto, Didier Schneiter, Isabelle Opitz, Hans Heinrich Jung, Antonio Lanzavecchia, Bettina Schreiner, and Burkhard Becher
Subjects: Immunology, Immunology and Allergy
Abstract: Myasthenia gravis is a rare but archetypic autoimmune disease that is characterized by the autoantibody-mediated disruption of the neuromuscular junction leading to a skeletal muscle weakness. Immunomodulatory treatment options for Myasthenia gravis patients are largely unspecific, include suppression of the entire immune compartment and are often accompanied by severe side effects. In order to identify novel biomarkers for more targeted and effective therapeutic approaches, we combined high-dimensional mass and flow cytometry with supervised and unsupervised machine-learning algorithms. Analysis of the peripheral immune compartment of Myasthenia gravis patients and healthy controls revealed a cellular immune signature consisting of inflammatory memory T helper cells with a defined cytokine profile. The abundance of the identified leukocytes in the blood strongly correlated with the patients clinical disease activity, far better than auto-Ab titers. Moreover, we were able to locate T cells with the defined signature enriched in the inflamed thymus of Myasthenia gravis patients – the key organ for the induction and maintenance of the autoimmune disease. Lastly, using an unbiased pattern recognition approach, we identified lymphomas in a subset of Myasthenia gravis patients, further highlighting the potential of the applied analysis tools.
Published: 2020

25. High dimensional cellular profiling of the myeloid compartment in the geriatric mouse model

Author: Sinduya Krishnarajah, Florian Ingelfinger, Ekaterina Friebel, Dilay Cansever, and Burkhard Becher
Subjects: Immunology, Immunology and Allergy
Abstract: Aging, and age-related physiological changes, have been heavily implicated in declining immune functions. Many of these changes to the immune system include changes to the myeloid subsets, which have been poorly studied so far. Myeloid cells play crucial roles in acute infection and are involved in antigen presentation to cells of the adaptive immune system. Consequently, deciphering these age-related mechanisms holds great potential for targeting age-related changes in immunity. Here, we developed a model to map age related phenotypic changes in the myeloid compartment in all immunologically relevant murine organs. Using mass cytometry analysis (CyTOF), we assessed over 35 cell surface parameters on myeloid cells using a geriatric healthy mouse model. Results indicates age-related changes affecting the frequency and cell surface density of lineage markers on myeloid cells. Concretely, we see significant changes to cellular frequencies and marker expression within various resident myeloid populations, and exemplar organs will be presented here. Such age-related patterns may contribute to the impaired immune decline observed in aging. We are currently continually expanding this study and will validate the implications of these findings using spectral flow cytometry analysis.
Published: 2020

26. Early Fate Defines Microglia and Non-parenchymal Brain Macrophage Development

Author: Aymeric Silvin, Shyam Prabhakar, Morgane Sonia Thion, Peter See, Wiebke Mildenberger, Sonia Garel, Florent Ginhoux, Sebastian G. Utz, Iva Lelios, Florian Ingelfinger, Anne Buttgereit, Mirjam Lutz, Kenichi Asano, Melanie Greter, Burkhard Becher, Nirmala Arul Rayan, Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Department of Computational and Systems Biology [Singapore], Genome Institute of Singapore (GIS), Bayer Pharma AG [Berlin], Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, and Greter, Melanie
Subjects: [SDV]Life Sciences [q-bio], medicine.medical_treatment, Central nervous system, 610 Medicine & health, Biology, 10263 Institute of Experimental Immunology, Monocytes, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, 1300 General Biochemistry, Genetics and Molecular Biology, Transforming Growth Factor beta, medicine, Animals, Macrophage, Cell Lineage, Progenitor cell, Yolk sac, Perivascular space, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Microglia, Macrophages, Brain, food and beverages, Cell biology, medicine.anatomical_structure, Cytokine, 570 Life sciences, biology, Choroid plexus, 030217 neurology & neurosurgery, Signal Transduction
Abstract: Central nervous system (CNS) macrophages comprise microglia and border-associated macrophages (BAMs) residing in the meninges, the choroid plexus, and the perivascular spaces. Most CNS macrophages emerge during development, with the exception of choroid plexus and dural macrophages, which are replaced by monocytes in adulthood. Whether microglia and BAMs share a developmental program or arise from separate lineages remains unknown. Here, we identified two phenotypically, transcriptionally, and locally distinct brain macrophages throughout development, giving rise to either microglia or BAMs. Two macrophage populations were already present in the yolk sac suggesting an early segregation. Fate-mapping models revealed that BAMs mostly derived from early erythro-myeloid progenitors in the yolk sac. The development of microglia was dependent on TGF-β, whereas the genesis of BAMs occurred independently of this cytokine. Collectively, our data show that developing parenchymal and non-parenchymal brain macrophages are separate entities in terms of ontogeny, gene signature, and requirement for TGF-β.
Published: 2020

27. GM-CSF: Master regulator of the T cell-phagocyte interface during inflammation

Author: 'Florian Ingelfinger

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27 results on '"Florian Ingelfinger"'

1. S257: CAR T CELLS AND THEIR IMMUNE ENVIRONMENT SHAPE DISTINCT IMMUNE PROFILES IN RESPONSE AND TOXICITY IN B CELL LYMPHOMA PATIENTS

2. S100A9 Drives the Chronification of Psoriasiform Inflammation by Inducing IL-23/Type 3 Immunity

3. Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates

4. Single-cell profiling of immune system alterations in lymphoid, barrier and solid tissues in aged mice

5. B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis

6. Neuroprotective tissue adaptation induced by IL-12 attenuates CNS inflammation

7. Embryonic and neonatal waves generate distinct populations of hepatic ILC1s

8. High-dimensional immune profiling identifies a biomarker to monitor dimethyl fumarate response in multiple sclerosis

9. CAR T Cells and Their Immune Environment Synergize to Shape Distinct Immune Profiles in Response Versus Toxicity in B Cell Lymphoma Patients

10. Immunological Predictors of Dimethyl Fumarate-Induced Lymphopenia

11. IFNγ and GM-CSF control complementary differentiation programs in the monocyte-to-phagocyte transition during neuroinflammation

12. Pre-existing comorbidities shape the immune response associated with severe COVID-19

13. Protection against autoimmunity is driven by thymic epithelial cell–mediated regulation of Tregdevelopment

14. Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of T

15. GM-CSF: Master regulator of the T cell-phagocyte interface during inflammation

16. IL-12 regulates type 3 immunity through interfollicular keratinocytes in psoriasiform inflammation

17. Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature

18. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

19. Single-cell multiomics in neuroinflammation

20. Twin study reveals non-heritable immune perturbations in multiple sclerosis

21. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

22. Correction to: Single‑cell profiling of myasthenia gravis identifies a pathogenic T cell signature

23. GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis

24. Myasthenia gravis: From single cell signatures to cancer diagnosis

25. High dimensional cellular profiling of the myeloid compartment in the geriatric mouse model

26. Early Fate Defines Microglia and Non-parenchymal Brain Macrophage Development

27. GM-CSF: Master regulator of the T cell-phagocyte interface during inflammation

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27 results on '"Florian Ingelfinger"'

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