肥胖会强化性别特异性干扰素信号,从而选择性地恶化女性中枢神经系统自身免疫。

Cell metabolism Pub Date : 2024-10-01 Epub Date: 2024-08-20 DOI:10.1016/j.cmet.2024.07.017
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
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引用次数: 0

摘要

肥胖与女性自身免疫性疾病的增加有关。我们报告说,在人类女性中,肥胖会诱导一种与T辅助细胞1(Th1)、白细胞介素(IL)-17和多发性硬化(MS)信号通路相关的血清蛋白特征。饮食诱导超重/肥胖(DIO)的雌性小鼠(而非雄性小鼠)在实验性自身免疫性脑脊髓炎(一种多发性硬化症模型)期间表现出中枢神经系统Th1/IL-17炎症上调。这与残疾恶化和外周淋巴器官中髓鞘特异性 Th1 细胞的扩增有关。此外,在稳定状态下,DIO能提高雌性小鼠血清中干扰素(IFN)-α的水平,并增强STAT1的表达和天真CD4+ T细胞产生的IFN-γ。这种T细胞表型是由脂肪增加驱动的,切除卵巢或敲除T细胞中的I型IFN受体可阻止这种表型。我们的发现从机理上解释了肥胖如何增强自身免疫力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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.

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