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IL-17A controls CNS autoimmunity by regulating gut microbiota and inducing regulatory T cells

ABSTRACT: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system. The pathogenesis of MS and other autoimmune diseases is defined by a disrupted equilibrium between IL-17A-producing CD4 T cells (Th17) and regulatory CD4 T cells (Treg). The development of Treg and Th17 cells can be regulated by the gut microbiota, however, it is unclear how the gut microbiota is impacted by IL-17A and how this, in turn, modulates Treg and disease. Here, we show that IL-17A deficiency promotes interferon-I-related gene expression and expands gut microbes that induce the Treg cells, resulting in milder disease in a mouse model of MS. Utilizing HLA-DR3.IL17A-/- transgenic mice, we showed significant enrichment of Treg-promoting gut microbes such as Prevotella sp. MGM1, Parabacteroides distasonis and Bacteroides sartorii species. Further, we observed enrichment of bacterial-specific short-chain fatty acid metabolic pathways that promote Treg function in HLA-DR3.IL17A-/- transgenic mice. Notably, disease severity was reversed in IL-17A sufficient mice that received fecal transplants from, and cohoused with, IL-17A-deficient mice, highlighting a critical role for the gut microbiota in inducing Treg and reducing disease severity. Collectively, we show that IL-17A is an important regulator of the gut microbiota-Treg axis, which mediates immune homeostasis, inflammation, and diseases such as MS.

ORGANISM(S): Mus musculus

PROVIDER: GSE190048 | GEO | 2025/10/01

REPOSITORIES: GEO

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