Obesity intensifies sex-specific interferon signaling to selectively worsen central nervous system autoimmunity in females

Brendan Cordeiro, Jeeyoon Jennifer Ahn, Saurabh Gawde, Carmen Ucciferri, Nuria Alvarez-Sanchez, Xavier S. Revelo, Natalie Stickle, Kaylea Massey, David G. Brooks, Joel M. Guthridge, Gabriel Pardo, Daniel A. Winer, Robert C. Axtell, Shannon E. Dunn

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 languageEnglish (US)
Pages (from-to)2298-2314.e11
JournalCell Metabolism
Volume36
Issue number10
DOIs
StatePublished - 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

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