微生物代谢物吲哚-3-丙酸驱动CD4+ T细胞的线粒体呼吸，以保护机体免受肠道炎症。

IF 20.8 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism Pub Date : 2025-10-21 DOI:10.1038/s42255-025-01396-6

Qing Li,Rodrigo de Oliveira Formiga,Virginie Puchois,Laura Creusot,Ahmad Haidar Ahmad,Salomé Amouyal,Márcio Augusto Campos-Ribeiro,Yining Zhao,Danielle M M Harris,Frederic Lasserre,Sandrine Ellero-Simatos,Hervé Guillou,Zhan Huang,Loic Brot,Yuhang Hu,Loic Chollet,Camille Danne,Cyril Scandola,Tatiana Ledent,Guillaume Chevreux,Rafael J Argüello,Marcelo De Carvalho Bittencourt,Jessica Bettinger,Maud D'Aveni-Piney,David Moulin,Stefan Schreiber,Konrad Aden,Nathalie Rolhion,Marie-Laure Michel,Timothy Wai,Harry Sokol

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引用次数: 0

摘要

肠道菌群及其代谢产物对免疫细胞的表型、功能和能量代谢具有重要的调节作用。我们筛选了一系列与肠道微生物群相关的代谢物，以鉴定T细胞中线粒体代谢的调节剂。本研究表明，吲哚-3-丙酸（IPA）通过增加脂肪酸氧化（FAO）和氨基酸氧化（AAO）来刺激CD4+ T细胞的线粒体呼吸，同时抑制糖酵解能力。IPA还通过抑制CD4+ T细胞向1型和17型辅助性T细胞表型的分化来影响其行为。机制上，IPA的代谢和免疫作用是由过氧化物酶体增殖物激活受体-β/δ介导的。IPA通过增强结肠CD4+ T细胞中的FAO和AAO来挽救肠道细菌耗尽或结肠炎小鼠的线粒体呼吸。过继性转移实验表明，IPA作用于CD4+ T细胞，发挥其抗炎症的保护作用。总的来说，我们的研究表明，IPA的抗炎作用是通过CD4+ T细胞的代谢重编程介导的，从而增强线粒体呼吸。

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Microbial metabolite indole-3-propionic acid drives mitochondrial respiration in CD4+ T cells to confer protection against intestinal inflammation.

The gut microbiota and its metabolites critically regulate immune cell phenotype, function and energy metabolism. We screened a collection of gut microbiota-related metabolites to identify modulators of mitochondrial metabolism in T cells. Here we show that indole-3-propionic acid (IPA) stimulates mitochondrial respiration of CD4+ T cells by increasing fatty acid oxidation (FAO) and amino acid oxidation (AAO), while inhibiting glycolytic capacity. IPA also impacts CD4+ T cell behaviour by inhibiting their differentiation to type 1 and type 17 helper T cell phenotypes. Mechanistically, the metabolic and immune effects of IPA are mediated by peroxisome proliferator-activated receptor-β/δ. The administration of IPA rescues mitochondria respiration in mice with gut bacteria depletion or colitis by enhancing FAO and AAO in colonic CD4+ T cells. Adoptive transfer experiments show that IPA acts on CD4+ T cells to exert its protective effect against inflammation. Collectively, our study reveals that the anti-inflammatory effects of IPA are mediated by metabolic reprogramming of CD4+ T cells toward the enhancement of mitochondrial respiration.

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来源期刊

Nature metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

27.50

自引率

2.40%

发文量

170

期刊介绍： Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.