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

Abstract

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:5 February 2021
Deposited On:18 Nov 2021 07:04
Last Modified:26 Oct 2024 01:38
Publisher:American Association for the Advancement of Science
ISSN:2470-9468
OA Status:Closed
Publisher DOI:https://doi.org/10.1126/sciimmunol.aaz6563
PubMed ID:33547052

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