Search

Your search keyword '"Martina Lubrano di Ricco"' showing total 3 results
Start Over Author "Martina Lubrano di Ricco" Topic autoimmunity
3 results on '"Martina Lubrano di Ricco"'

1. The NF-κB RelA Transcription Factor Is Critical for Regulatory T Cell Activation and Stability

Author

Emilie Ronin, Martina Lubrano di Ricco, Romain Vallion, Jordane Divoux, Ho-Keun Kwon, Sylvie Grégoire, Davi Collares, Angéline Rouers, Véronique Baud, Christophe Benoist, and Benoit L. Salomon

Subjects
regulatory T cells, NF-κB, autoimmunity, stability, activation, relA, Immunologic diseases. Allergy, RC581-607
Abstract

Regulatory T cells (Tregs) play a major role in immune homeostasis and in the prevention of autoimmune diseases. It has been shown that c-Rel is critical in Treg thymic differentiation, but little is known on the role of NF-κB on mature Treg biology. We thus generated mice with a specific knockout of RelA, a key member of NF-κB, in Tregs. These mice developed a severe autoimmune syndrome with multi-organ immune infiltration and high activation of lymphoid and myeloid cells. Phenotypic and transcriptomic analyses showed that RelA is critical in the acquisition of the effector Treg state independently of surrounding inflammatory environment. Unexpectedly, RelA-deficient Tregs also displayed reduced stability and cells that had lost Foxp3 produced inflammatory cytokines. Overall, we show that RelA is critical for Treg biology as it promotes both the generation of their effector phenotype and the maintenance of their identity.

Published
2019
Full Text
View/download PDF

2. Regulatory T Cell Stability and Migration Are Dependent on mTOR

Author

Bruno Lucas, Ivan Nemazanyy, Sylvie Grégoire, Benoît L. Salomon, Emilie Ronin, Aurélie Durand, Salomé Glauzy, Martina Lubrano di Ricco, Jordane Divoux, Romain Vallion, Delphine Fradin, Yannis Lombardi, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Fondation pour la Recherche Médicale (Equipes FRM 2015)Fondation Bettencourt Schueller (Coups d’Elan pour la Recherche Française)Association de la Recherche sur la Sclérose en PlaquesRégion Ile-de-France (CORDDIM), ANR-17-CE15-0030,MetaTreg,Métabolisme cellulaire des Treg dans le controle des maladies inflammatoires chroniques(2017), Bernardo, Elizabeth, Métabolisme cellulaire des Treg dans le controle des maladies inflammatoires chroniques - - MetaTreg2017 - ANR-17-CE15-0030 - AAPG2017 - VALID, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Regulatory T cell, Cellular differentiation, Glutamine, Immunology, chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer, Autoimmunity, Biology, Lymphocyte Activation, T-Lymphocytes, Regulatory, Immune tolerance, 03 medical and health sciences, Mice, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, medicine, Immunology and Allergy, Animals, Mechanistic target of rapamycin, PI3K/AKT/mTOR pathway, Inflammation, Mice, Knockout, Glutaminolysis, TOR Serine-Threonine Kinases, FOXP3, hemic and immune systems, Cell Differentiation, Forkhead Transcription Factors, DNA Methylation, medicine.anatomical_structure, Mutation, biology.protein, Cancer research, Signal transduction, 030215 immunology, Signal Transduction
Abstract

CD4+ Foxp3+ regulatory T cells (Treg) are essential to maintain immune tolerance, as their loss leads to a fatal autoimmune syndrome in mice and humans. Conflicting findings have been reported concerning their metabolism. Some reports found that Treg have low mechanistic target of rapamycin (mTOR) activity and would be less dependent on this kinase compared with conventional T cells, whereas other reports suggest quite the opposite. In this study, we revisited this question by using mice that have a specific deletion of mTOR in Treg. These mice spontaneously develop a severe and systemic inflammation. We show that mTOR expression by Treg is critical for their differentiation into effector Treg and their migration into nonlymphoid tissues. We also reveal that mTOR-deficient Treg have reduced stability. This loss of Foxp3 expression is associated with partial Foxp3 DNA remethylation, which may be due to an increased activity of the glutaminolysis pathway. Thus, our work shows that mTOR is crucial for Treg differentiation, migration, and identity and that drugs targeting this metabolism pathway will impact on their biology.

Published
2019

3. A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity

Author

Martina Lubrano Di Ricco, William Ruff, Rebecca L. Fine, Teri M. Greiling, Carina Dehner, Alonso J. Iñiguez, John Sterpka, Silvio M. Vieira, Derek L. Mubiru, Daniel F. Zegarra-Ruiz, Asmaa El Beidaq, and Martin A. Kriegel

Subjects
Limosilactobacillus reuteri, Chromosomal translocation, Autoimmunity, Gut flora, medicine.disease_cause, Kidney, Feces, Mice, 0302 clinical medicine, Glomerulonephritis, Interferon, Lactobacillus, RNA, Ribosomal, 16S, Lupus Erythematosus, Systemic, Receptor, 0303 health sciences, Membrane Glycoproteins, biology, food and beverages, Starch, Survival Rate, Interferon Type I, Female, medicine.drug, Clostridiaceae, Microbiology, DNA, Ribosomal, 03 medical and health sciences, Virology, medicine, Hypersensitivity, Animals, Germ-Free Life, Humans, 030304 developmental biology, TLR7, Dendritic Cells, biology.organism_classification, Fatty Acids, Volatile, Lactobacillus reuteri, Diet, Gastrointestinal Microbiome, Mice, Inbred C57BL, Disease Models, Animal, Toll-Like Receptor 7, Immunology, Parasitology, 030217 neurology & neurosurgery, Diet Therapy
Abstract

Summary Western lifestyle is linked to autoimmune and metabolic diseases, driven by changes in diet and gut microbiota composition. Using Toll-like receptor 7 (TLR7)-dependent mouse models of systemic lupus erythematosus (SLE), we dissect dietary effects on the gut microbiota and find that Lactobacillus reuteri can drive autoimmunity but is ameliorated by dietary resistant starch (RS). Culture of internal organs and 16S rDNA sequencing revealed TLR7-dependent translocation of L. reuteri in mice and fecal enrichment of Lactobacillus in a subset of SLE patients. L. reuteri colonization worsened autoimmune manifestations under specific-pathogen-free and gnotobiotic conditions, notably increasing plasmacytoid dendritic cells (pDCs) and interferon signaling. However, RS suppressed the abundance and translocation of L. reuteri via short-chain fatty acids, which inhibited its growth. Additionally, RS decreased pDCs, interferon pathways, organ involvement, and mortality. Thus, RS exerts beneficial effects in lupus-prone hosts through suppressing a pathobiont that promotes interferon pathways implicated in the pathogenesis of human autoimmunity.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results