MAIT cells monitor intestinal dysbiosis and contribute to host protection during colitis

IF 17.6 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2024-06-21 DOI:10.1126/sciimmunol.adi8954

Yara El Morr, Mariela Fürstenheim, Martin Mestdagh, Katarzyna Franciszkiewicz, Marion Salou, Claire Morvan, Thierry Dupré, Alexey Vorobev, Bakhos Jneid, Virginie Premel, Aurélie Darbois, Laetitia Perrin, Stanislas Mondot, Ludovic Colombeau, Hélène Bugaut, Anastasia du Halgouet, Sophie Richon, Emanuele Procopio, Mathieu Maurin, Catherine Philippe, Raphael Rodriguez, Olivier Lantz, François Legoux

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引用次数: 0

Abstract

Intestinal inflammation shifts microbiota composition and metabolism. How the host monitors and responds to such changes remains unclear. Here, we describe a protective mechanism by which mucosal-associated invariant T (MAIT) cells detect microbiota metabolites produced upon intestinal inflammation and promote tissue repair. At steady state, MAIT ligands derived from the riboflavin biosynthesis pathway were produced by aerotolerant bacteria residing in the colonic mucosa. Experimental colitis triggered luminal expansion of riboflavin-producing bacteria, leading to increased production of MAIT ligands. Modulation of intestinal oxygen levels suggested a role for oxygen in inducing MAIT ligand production. MAIT ligands produced in the colon rapidly crossed the intestinal barrier and activated MAIT cells, which expressed tissue-repair genes and produced barrier-promoting mediators during colitis. Mice lacking MAIT cells were more susceptible to colitis and colitis-driven colorectal cancer. Thus, MAIT cells are sensitive to a bacterial metabolic pathway indicative of intestinal inflammation.

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MAIT 细胞能监测肠道菌群失调，并在结肠炎期间为宿主提供保护。

肠道炎症会改变微生物群的组成和新陈代谢。宿主如何监测和应对这种变化仍不清楚。在这里，我们描述了一种保护机制，通过这种机制，粘膜相关不变T（MAIT）细胞能检测到肠道炎症时产生的微生物群代谢产物，并促进组织修复。在稳定状态下，结肠粘膜中的耐气细菌会产生核黄素生物合成途径衍生的 MAIT 配体。实验性结肠炎会引发产生核黄素的细菌在管腔内扩张，从而导致 MAIT 配体的产生增加。对肠道氧气水平的调节表明，氧气在诱导 MAIT 配体的产生方面发挥了作用。结肠中产生的 MAIT 配体迅速穿过肠道屏障并激活 MAIT 细胞，这些细胞表达组织修复基因，并在结肠炎期间产生促进屏障的介质。缺乏 MAIT 细胞的小鼠更容易患结肠炎和结肠炎导致的结直肠癌。因此，MAIT细胞对表明肠道炎症的细菌代谢途径很敏感。

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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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.