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23 results on '"Culemann, Stephan"'

1. IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation

Author

Faas, Maria, Ipseiz, Natacha, Ackermann, Jochen, Culemann, Stephan, Grüneboom, Anika, Schröder, Fenja, Rothe, Tobias, Scholtysek, Carina, Eberhardt, Martin, Böttcher, Martin, Kirchner, Philipp, Stoll, Cornelia, Ekici, Arif, Fuchs, Maximilian, Kunz, Meik, Weigmann, Benno, Wirtz, Stefan, Lang, Roland, Hofmann, Joerg, Vera, Julio, Voehringer, David, Michelucci, Alessandro, Mougiakakos, Dimitrios, Uderhardt, Stefan, Schett, Georg, and Krönke, Gerhard

Published
2021
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2. Locally renewing resident synovial macrophages provide a protective barrier for the joint

Author

Culemann, Stephan, Grüneboom, Anika, Nicolás-Ávila, José Ángel, Weidner, Daniela, Lämmle, Katrin Franziska, Rothe, Tobias, and Quintana, Juan A.

Subjects
Physiological aspects, Genetic aspects, Rheumatoid arthritis -- Physiological aspects, Macrophages -- Physiological aspects -- Genetic aspects, RNA sequencing
Abstract

Author(s): Stephan Culemann [sup.1] [sup.2] , Anika Grüneboom [sup.1] [sup.2] , José Ángel Nicolás-Ávila [sup.3] , Daniela Weidner [sup.1] [sup.2] , Katrin Franziska Lämmle [sup.1] [sup.2] , Tobias Rothe [sup.1] [...], Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis.sup.1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis. We find that dynamic membrane-like structures, consisting of a distinct population of CX.sub.3CR1.sup.+ tissue-resident macrophages, form an internal immunological barrier at the synovial lining and physically seclude the joint. These barrier-forming macrophages display features that are otherwise typical of epithelial cells, and maintain their numbers through a pool of locally proliferating CX.sub.3CR1.sup.- mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX.sub.3CR1.sup.+ lining macrophages restrict the inflammatory reaction by providing a tight-junction-mediated shield for intra-articular structures. Our data reveal an unexpected functional diversification among synovial macrophages and have important implications for the general role of macrophages in health and disease. Analysis of macrophage subsets within joints reveals a population of CX.sub.3CR1.sup.+ tissue-resident macrophages that form a tight-junction-mediated barrier at the synovial lining, protecting the joint from the invasion of inflammatory cells.

Published
2019
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3. A network of trans-cortical capillaries as mainstay for blood circulation in long bones

Author

Grüneboom, Anika, Hawwari, Ibrahim, Weidner, Daniela, Culemann, Stephan, Müller, Sylvia, Henneberg, Sophie, Brenzel, Alexandra, Merz, Simon, Bornemann, Lea, Zec, Kristina, Wuelling, Manuela, Kling, Lasse, Hasenberg, Mike, Voortmann, Sylvia, Lang, Stefanie, Baum, Wolfgang, Ohs, Alexandra, Kraff, Oliver, Quick, Harald H., Jäger, Marcus, Landgraeber, Stefan, Dudda, Marcel, Danuser, Renzo, Stein, Jens V., Rohde, Manfred, Gelse, Kolja, Garbe, Annette I., Adamczyk, Alexandra, Westendorf, Astrid M., Hoffmann, Daniel, Christiansen, Silke, Engel, Daniel Robert, Vortkamp, Andrea, Krönke, Gerhard, Herrmann, Martin, Kamradt, Thomas, Schett, Georg, Hasenberg, Anja, and Gunzer, Matthias

Published
2019
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4. Addendum: Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes

Author

Culemann, Stephan, primary, Knab, Katharina, additional, Euler, Maximilien, additional, Wegner, Anja, additional, Garibagaoglu, Hilal, additional, Ackermann, Jochen, additional, Fischer, Kim, additional, Kienhöfer, Deborah, additional, Crainiciuc, Georgiana, additional, Hahn, Jonas, additional, Grüneboom, Anika, additional, Nimmerjahn, Falk, additional, Uderhardt, Stefan, additional, Hidalgo, Andrés, additional, Schett, Georg, additional, Hoffmann, Markus H., additional, and Krönke, Gerhard, additional

Published
2023
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6. Stunning of neutrophils accounts for the anti-inflammatory effects of clodronate liposomes

Author

Culemann, Stephan, primary, Knab, Katharina, additional, Euler, Maximilien, additional, Wegner, Anja, additional, Garibagaoglu, Hilal, additional, Ackermann, Jochen, additional, Fischer, Kim, additional, Kienhöfer, Deborah, additional, Crainiciuc, Georgiana, additional, Hahn, Jonas, additional, Grüneboom, Anika, additional, Nimmerjahn, Falk, additional, Uderhardt, Stefan, additional, Hidalgo, Andrés, additional, Schett, Georg, additional, Hoffmann, Markus H., additional, and Krönke, Gerhard, additional

Published
2023
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10. Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis

Author

Tajik, Narges, primary, Frech, Michael, additional, Schulz, Oscar, additional, Schälter, Fabian, additional, Lucas, Sébastien, additional, Azizov, Vugar, additional, Dürholz, Kerstin, additional, Steffen, Franziska, additional, Omata, Yasunori, additional, Rings, Andreas, additional, Bertog, Marko, additional, Rizzo, Aroldo, additional, Iljazovic, Aida, additional, Basic, Marijana, additional, Kleyer, Arnd, additional, Culemann, Stephan, additional, Krönke, Gerhard, additional, Luo, Yubin, additional, Überla, Klaus, additional, Gaipl, Udo S., additional, Frey, Benjamin, additional, Strowig, Till, additional, Sarter, Kerstin, additional, Bischoff, Stephan C., additional, Wirtz, Stefan, additional, Cañete, Juan D., additional, Ciccia, Francesco, additional, Schett, Georg, additional, and Zaiss, Mario M., additional

Published
2020
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11. Charakterisierung der Entwicklung und Funktion synovialer Makrophagen

Author

Culemann, Stephan

Subjects
Medizinische Fakultät, ddc:570, Naturwissenschaftliche Fakultät
Abstract

Rheumatoide Arthritis (RA) ist eine der häufigsten Autoimmunerkrankungen in unserer Gesellschaft und geht mit starken Schmerzen und motorischen Behinderungen einher. Die RA ist vor allem durch chronische Entzündungen der synovialen Gelenke gekennzeichnet. Unbehandelt führt sie schließlich zum vollständigen Funktionsverlust der Gelenke. Eine Vielzahl von Immunzellen sind in die Pathogenese der RA involviert, wobei Makrophagen eine besondere Rolle im Entzündungsprozess spielen. Mit Hilfe konditionaler, transgener Mäuse, hochauflösender und dreidimensionaler Bildgebung sowie neuester Sequenzierungstechniken zur Erstellung von Transkriptionsprofilen wurden die mikroanatomische Organisation, Ontogenese und Differenzierung von unterschiedlichen synovialen Makrophagen-Populationen sowie deren funktionelle Rolle im gesunden und entzündeten Gelenk untersucht. So konnte gezeigt werden, dass eine besondere Population von gewebsresidenten CX3CR1+ Makrophagen in der synovialen Intima der Gelenke eine dynamische Membran bilden, welche das umgebene synoviale Gewebe von der Gelenkflüssigkeit trennt und als immunologische Barriere fungiert. CX3CR1+ Makrophagen und eine weitere Subpopulation interstitieller Makrophagen, welche einen alternativ aktivierten Phänotyp aufweisen, gehen aus einem residenten Pool proliferierender CX3CR1- CSF1R+ Makrophagenvorläufer hervor, die sich im interstitiellen Synovialgewebe befinden. Im Falle einer Gelenksentzündung kommt es zum Aufbrechen der Makrophagenbarriere, die unter physiologischen Bedingungen durch Tight Junctions und Desmosomen stabilisiert wird. Infiltrierende Makrophagen, die sich von Kochenmarkszellen ableiten, infiltrieren das Synovialgewebe und treiben die Entzündung voran. Pharmakologische Destabilisierung oder Stabilisierung der Tight Junctions legen eine protektive Funktion der Makrophagenbarriere nahe. Im Gegensatz zur Depletion von Blutmonozyten, führte der Verlust der Synovialmakrophagen zu einer Exazerbation Antiköper-vermittelter Gelenksentzündungen und bestätigte die entzündungs-eindämmende Funktion der Synovialmakrophagen. Diese Dissertation erweitert somit maßgeblich das grundlegende Verständnis über die Diversität, Ontogenese sowie Funktion synovialer Makrophagen unter physiologischen und entzündlichen Bedingungen und setzt sie in einen mikroanatomischen Kontext.

Published
2020

13. JAK inhibition increases bone mass in steady-state conditions and ameliorates pathological bone loss by stimulating osteoblast function

Author

Adam, Susanne, primary, Simon, Nils, additional, Steffen, Ulrike, additional, Andes, Fabian T., additional, Scholtysek, Carina, additional, Müller, Dorothea I. H., additional, Weidner, Daniela, additional, Andreev, Darja, additional, Kleyer, Arnd, additional, Culemann, Stephan, additional, Hahn, Madelaine, additional, Schett, Georg, additional, Krönke, Gerhard, additional, Frey, Silke, additional, and Hueber, Axel J., additional

Published
2020
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14. OP0076 JAK-INHIBITORS TOFACITINIB AND BARICITINIB IMPROVE PATHOLOGICAL BONE LOSS IN VIVO

Author

Adam, Susanne, primary, Simon, Nils, additional, Steffen, Ulrike, additional, Harre, Née, additional, Andes, Fabian, additional, Müller, Dorothea, additional, Culemann, Stephan, additional, Andreev, Darja, additional, Hahn, Madelaine, additional, Scholtysek, Carina, additional, Schett, Georg, additional, Krönke, Gerhard, additional, Frey, Silke, additional, and Hueber, Axel, additional

Published
2019
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19. Regulation of autoantibody activity by the IL-23–TH17 axis determines the onset of autoimmune disease

Author

Pfeifle, René, primary, Rothe, Tobias, additional, Ipseiz, Natacha, additional, Scherer, Hans U, additional, Culemann, Stephan, additional, Harre, Ulrike, additional, Ackermann, Jochen A, additional, Seefried, Martina, additional, Kleyer, Arnd, additional, Uderhardt, Stefan, additional, Haugg, Benjamin, additional, Hueber, Axel J, additional, Daum, Patrick, additional, Heidkamp, Gordon F, additional, Ge, Changrong, additional, Böhm, Sybille, additional, Lux, Anja, additional, Schuh, Wolfgang, additional, Magorivska, Iryna, additional, Nandakumar, Kutty S, additional, Lönnblom, Erik, additional, Becker, Christoph, additional, Dudziak, Diana, additional, Wuhrer, Manfred, additional, Rombouts, Yoann, additional, Koeleman, Carolien A, additional, Toes, René, additional, Winkler, Thomas H, additional, Holmdahl, Rikard, additional, Herrmann, Martin, additional, Blüml, Stephan, additional, Nimmerjahn, Falk, additional, Schett, Georg, additional, and Krönke, Gerhard, additional

Published
2016
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20. Novel mechanisms of action and new target genes of the glucocorticoid receptor in inflammatory bone disease and bone loss

Author

Baschant, Ulrike, primary, Ahmad, Mubashir, additional, Koenen, Mascha, additional, Knoll, Jeanette, additional, Culemann, Stephan, additional, Schauer, Sebastian, additional, Bauer, Kerstin, additional, Wittig-Blaich, Stephanie, additional, Rauch, Alexander, additional, Kronke, Gehrhard, additional, Dudeck, Anne, additional, David, Jean-Pierre, additional, Rauner, Martina, additional, Seibel, Markus, additional, Ploubidou, Aspasia, additional, Zhou, Hong, additional, Hofbauer, Lorenz, additional, and Tuckermann, Jan, additional

Published
2014
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22. Regulation of autoantibody activity by the IL-23-T H 17 axis determines the onset of autoimmune disease.

Author

Pfeifle R, Rothe T, Ipseiz N, Scherer HU, Culemann S, Harre U, Ackermann JA, Seefried M, Kleyer A, Uderhardt S, Haugg B, Hueber AJ, Daum P, Heidkamp GF, Ge C, Böhm S, Lux A, Schuh W, Magorivska I, Nandakumar KS, Lönnblom E, Becker C, Dudziak D, Wuhrer M, Rombouts Y, Koeleman CA, Toes R, Winkler TH, Holmdahl R, Herrmann M, Blüml S, Nimmerjahn F, Schett G, and Krönke G

Subjects
Animals, Cell Differentiation, Cells, Cultured, Disease Models, Animal, Glycosylation, Humans, Interleukins metabolism, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Sialyltransferases genetics, Sialyltransferases metabolism, Signal Transduction, beta-D-Galactoside alpha 2-6-Sialyltransferase, Interleukin-22, Interleukin-21, Arthritis, Rheumatoid immunology, Autoantibodies metabolism, B-Lymphocytes immunology, Immune Tolerance, Immunoglobulin G metabolism, Interleukin-23 metabolism, Th17 Cells immunology
Abstract

The checkpoints and mechanisms that contribute to autoantibody-driven disease are as yet incompletely understood. Here we identified the axis of interleukin 23 (IL-23) and the T H 17 subset of helper T cells as a decisive factor that controlled the intrinsic inflammatory activity of autoantibodies and triggered the clinical onset of autoimmune arthritis. By instructing B cells in an IL-22- and IL-21-dependent manner, T H 17 cells regulated the expression of β-galactoside α2,6-sialyltransferase 1 in newly differentiating antibody-producing cells and determined the glycosylation profile and activity of immunoglobulin G (IgG) produced by the plasma cells that subsequently emerged. Asymptomatic humans with rheumatoid arthritis (RA)-specific autoantibodies showed identical changes in the activity and glycosylation of autoreactive IgG antibodies before shifting to the inflammatory phase of RA; thus, our results identify an IL-23-T H 17 cell-dependent pathway that controls autoantibody activity and unmasks a preexisting breach in immunotolerance., Competing Interests: The authors declare no competing financial interests.

Published
2017
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23. Adopted orphans as regulators of inflammation, immunity and skeletal homeostasis.

Author

Ipseiz N, Scholtysek C, Culemann S, and Krönke G

Subjects
Adaptive Immunity, Bone Remodeling, Homeostasis, Humans, Immunity, Innate, Inflammation metabolism, Liver X Receptors, Bone and Bones physiology, Orphan Nuclear Receptors metabolism, Peroxisome Proliferator-Activated Receptors metabolism
Abstract

Adopted orphan nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs), have emerged as key regulators of inflammation and immunity and likewise control skeletal homeostasis. These properties render them attractive targets for the therapy of various inflammatory and autoimmune diseases affecting the musculoskeletal system. This review summarises the current knowledge on the role of these families of receptors during innate and adaptive immunity as well as during the control of bone turnover and discuss the potential use of targeting these molecules during the treatment of chronic diseases such as osteoarthritis, rheumatoid arthritis and osteoporosis.

Published
2014
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