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Regen, T.* ; Isaac, S.* ; Amorim, A.* ; Núñez, N.G.* ; Hauptmann, J.* ; Shanmugavadivu, A.* ; Klein, M.* ; Sankowski, R.* ; Mufazalov, I.A.* ; Yogev, N.* ; Huppert, J.* ; Wanke, F.* ; Witting, M. ; Grill, A.* ; Gálvez, E.J.C.* ; Nikolaev, A.* ; Blanfeld, M.* ; Prinz, I.* ; Schmitt-Kopplin, P. ; Strowig, T.* ; Reinhardt, C.* ; Prinz, M.* ; Bopp, T.* ; Becher, B.* ; Ubeda, C.* ; Waisman, A.*

IL-17 controls central nervous system autoimmunity through the intestinal microbiome.

Sci. Immunol. 6:eaaz6563 (2021)
DOI Verlagsversion bestellen
Interleukin-17A- (IL-17A) and IL-17F-producing CD4+ T helper cells (TH17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). TH17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, TH17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which correlated with an altered composition of their gut microbiota. However, loss of IL-17A/F in TH cells did not diminish their encephalitogenic capacity. Reconstitution of a wild-type-like intestinal microbiota or reintroduction of IL-17A specifically into the gut epithelium of IL-17A/F-deficient mice reestablished their susceptibility to EAE. Thus, our data demonstrated that IL-17A and IL-17F are not encephalitogenic mediators but rather modulators of intestinal homeostasis that indirectly alter CNS-directed autoimmunity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gut Microbiota; T-cells; Interleukin-17; Cns; Neutralization; Sequences; Cytokine; Receptor
ISSN (print) / ISBN 2470-9468
e-ISSN 2470-9468
Zeitschrift Science immunology
Quellenangaben Band: 6, Heft: 56, Seiten: , Artikelnummer: eaaz6563 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC
Begutachtungsstatus Peer reviewed
Förderungen Center for Molecular Medicine Cologne
Stiftung Rheinland-Pfalz fur Innovation
Hertie Foundation
Sobek Foundation
DFG
Research Center for Immunotherapy (FZI) Mainz
MINECO
MINECO FPI predoctoral fellowship
BMBF
Ministry of Science, Research and Arts, Baden-Wurttemberg (Sonderlinie "Neuroinflammation")
Ernst-Jung Foundation
European Union FP7 Project NeuroKine
Swiss National Science Foundation
National Multiple Sclerosis Society