饮食热量限制通过调节Teff/Treg平衡保护实验性自身免疫性葡萄膜炎

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2024-10-28 DOI:10.1016/j.isci.2024.111279

Zhaohuai Li , Runping Duan , Qi Jiang , Jiaying Liu , Jialing Chen , Loujing Jiang , Tianfu Wang , He Li , Yihan Zhang , Xuening Peng , Zhaohao Huang , Lei Zhu , Wenjun Zou , Ying Lin , Wenru Su

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引用次数: 0

摘要

葡萄膜炎是一种自身免疫性疾病，通常会导致失明。CD4+ T细胞，包括调节性T细胞（Tregs）和效应T细胞（Th1和Th17），在其发病机制中起着至关重要的作用。热量限制（CR）已被证明可以缓解自身免疫性疾病。然而，人们对热量限制对实验性自身免疫性葡萄膜炎（EAU）的影响还知之甚少。本研究使用单细胞 RNA 测序分析了小鼠在自由饮食（AL）和 CR 饮食条件下，有或没有 EAU 的颈部引流淋巴结。CR增加了Tregs，改变了免疫细胞代谢，减轻了EAU症状，并下调了炎症和糖酵解基因。流式细胞术证实了CR对Th1和Th17增殖的抑制作用以及对Treg增殖的促进作用。CR 还通过抑制 PI3K/AKT/c-Myc 通路和减少 Th17 细胞中的 GM-CSF 来平衡 CD4+ T 细胞。这些发现表明，CR 是治疗自身免疫性疾病的一种潜在策略。

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Dietary caloric restriction protects experimental autoimmune uveitis by regulating Teff/Treg balance

Uveitis, an autoimmune disease, often leads to blindness. CD4⁺ T cells, including regulatory T cells (Tregs) and effector T cells (Th1 and Th17), play a critical role in its pathogenesis. Caloric restriction (CR) has been shown to alleviate autoimmune diseases. However, careful characterization of the impact of CR on experimental autoimmune uveitis (EAU) is poorly understood. This study used single-cell RNA sequencing to analyze cervical draining lymph nodes in mice under ad libitum (AL) and CR diets, with or without EAU. CR increased Tregs, altered immune cell metabolism, reduced EAU symptoms, and downregulated inflammatory and glycolysis genes. Flow cytometry confirmed CR’s inhibitory effect on Th1 and Th17 proliferation and its promotion of Treg proliferation. CR also balanced CD4⁺ T cells by inhibiting the PI3K/AKT/c-Myc pathway and reducing GM-CSF in Th17 cells. These findings suggest CR as a potential therapeutic strategy for autoimmune diseases.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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