Abstract
Obesity has been implicated in the rise of autoimmunity in women. We report that obesity induces a serum protein signature that is associated with T helper 1 (Th1), interleukin (IL)-17, and multiple sclerosis (MS) signaling pathways selectively in human females. Females, but not male mice, subjected to diet-induced overweightness/obesity (DIO) exhibited upregulated Th1/IL-17 inflammation in the central nervous system during experimental autoimmune encephalomyelitis, a model of MS. This was associated with worsened disability and a heightened expansion of myelin-specific Th1 cells in the peripheral lymphoid organs. Moreover, at steady state, DIO increased serum levels of interferon (IFN)-α and potentiated STAT1 expression and IFN-γ production by naive CD4+ T cells uniquely in female mice. This T cell phenotype was driven by increased adiposity and was prevented by the removal of ovaries or knockdown of the type I IFN receptor in T cells. Our findings offer a mechanistic explanation of how obesity enhances autoimmunity.
Original language | English (US) |
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Pages (from-to) | 2298-2314.e11 |
Journal | Cell Metabolism |
Volume | 36 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2024 |
Bibliographical note
Publisher Copyright:© 2024
Keywords
- autoimmunity
- experimental autoimmune encephalomyelitis
- interferon-α
- multiple sclerosis
- obesity
- sex differences
- T cells
- T helper 1 differentiation
PubMed: MeSH publication types
- Journal Article