CD4+ T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival
Por:
Yogev N, Bedke T, Kobayashi Y, Brockmann L, Lukas D, Regen T, Croxford AL, Nikolav A, Hövelmeyer N, von Stebut E, Prinz M, Ubeda C, Maloy KJ, Gagliani N, Flavell RA, Waisman A and Huber S
Publicada:
29 mar 2022
Ahead of Print:
1 mar 2022
Categoría:
Biochemistry, genetics and molecular biology (miscellaneous)
Resumen:
Interleukin (IL)-10 is considered a prototypical anti-inflammatory cytokine, significantly contributing to the maintenance and reestablishment of immune homeostasis. Accordingly, it has been shown in the intestine that IL-10 produced by Tregs can act on effector T cells, thereby limiting inflammation. Herein, we investigate whether this role also applies to IL-10 produced by T cells during central nervous system (CNS) inflammation. During neuroinflammation, both CNS-resident and-infiltrating cells produce IL-10; yet, as IL-10 has a pleotropic function, the exact contribution of the different cellular sources is not fully understood. We find that T-cell-derived IL-10, but not other relevant IL-10 sources, can promote inflammation in experimental autoimmune encephalomyelitis. Furthermore, in the CNS, T-cell-derived IL-10 acts on effector T cells, promoting their survival and thereby enhancing inflammation and CNS autoimmunity. Our data indicate a pro -inflammatory role of T-cell-derived IL-10 in the CNS.
Filiaciones:
Yogev N:
Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Department of Dermatology and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine, University Hospital of Cologne, 50937 Cologne, Germany
Bedke T:
Hamburg Center for Translational Immunology (HCTI) and Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Kobayashi Y:
Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA
Brockmann L:
Hamburg Center for Translational Immunology (HCTI) and Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Lukas D:
Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Department of Dermatology and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine, University Hospital of Cologne, 50937 Cologne, Germany
Regen T:
Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Croxford AL:
Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Nikolav A:
Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Hövelmeyer N:
Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany
von Stebut E:
Department of Dermatology and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine, University Hospital of Cologne, 50937 Cologne, Germany
Prinz M:
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany
:
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana - FISABIO, Valencia, Spain
Maloy KJ:
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
Gagliani N:
Hamburg Center for Translational Immunology (HCTI) and Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute and University Hospital, 17176 Stockholm, Sweden
Flavell RA:
Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
Waisman A:
Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany
Focus Program Translational Neurosciences, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
Huber S:
Hamburg Center for Translational Immunology (HCTI) and Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany. Electronic address:
Green Accepted, gold
|