Signals that control MAIT cell function in healthy and inflamed human tissues

IF 7.5 2区 医学 Q1 IMMUNOLOGY Immunological Reviews Pub Date : 2024-03-22 DOI:10.1111/imr.13325
Andrew J. Konecny, Yin Huang, Manu Setty, Martin Prlic
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Abstract

Mucosal-associated invariant T (MAIT) cells have a semi-invariant T-cell receptor that allows recognition of antigen in the context of the MHC class I-related (MR1) protein. Metabolic intermediates of the riboflavin synthesis pathway have been identified as MR1-restricted antigens with agonist properties. As riboflavin synthesis occurs in many bacterial species, but not human cells, it has been proposed that the main purpose of MAIT cells is antibacterial surveillance and protection. The majority of human MAIT cells secrete interferon-gamma (IFNg) upon activation, while some MAIT cells in tissues can also express IL-17. Given that MAIT cells are present in human barrier tissues colonized by a microbiome, MAIT cells must somehow be able to distinguish colonization from infection to ensure effector functions are only elicited when necessary. Importantly, MAIT cells have additional functional properties, including the potential to contribute to restoring tissue homeostasis by expression of CTLA-4 and secretion of the cytokine IL-22. A recent study provided compelling data indicating that the range of human MAIT cell functional properties is explained by plasticity rather than distinct lineages. This further underscores the necessity to better understand how different signals regulate MAIT cell function. In this review, we highlight what is known in regards to activating and inhibitory signals for MAIT cells with a specific focus on signals relevant to healthy and inflamed tissues. We consider the quantity, quality, and the temporal order of these signals on MAIT cell function and discuss the current limitations of computational tools to extrapolate which signals are received by MAIT cells in human tissues. Using lessons learned from conventional CD8 T cells, we also discuss how TCR signals may integrate with cytokine signals in MAIT cells to elicit distinct functional states.

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控制健康和发炎人体组织中 MAIT 细胞功能的信号。
粘膜相关不变性 T 细胞(MAIT)具有一种半不变性 T 细胞受体,可在 MHC I 类相关蛋白(MR1)的背景下识别抗原。核黄素合成途径的代谢中间产物已被确定为具有激动特性的 MR1 限制性抗原。由于核黄素合成发生在许多细菌物种中,但不发生在人体细胞中,因此有人认为 MAIT 细胞的主要作用是抗菌监测和保护。大多数人类 MAIT 细胞在激活后会分泌γ 干扰素(IFNg),而组织中的一些 MAIT 细胞也能表达 IL-17。鉴于 MAIT 细胞存在于被微生物群定植的人体屏障组织中,MAIT 细胞必须能够以某种方式区分定植和感染,以确保只在必要时激发效应功能。重要的是,MAIT 细胞还具有其他功能特性,包括可能通过表达 CTLA-4 和分泌细胞因子 IL-22 来帮助恢复组织稳态。最近的一项研究提供了令人信服的数据,表明人类 MAIT 细胞功能特性的范围是由可塑性而非独特的血统所决定的。这进一步强调了更好地了解不同信号如何调控 MAIT 细胞功能的必要性。在这篇综述中,我们将重点介绍目前已知的 MAIT 细胞激活和抑制信号,并特别关注与健康和炎症组织相关的信号。我们考虑了这些信号对 MAIT 细胞功能的数量、质量和时间顺序,并讨论了目前计算工具在推断 MAIT 细胞在人体组织中接收哪些信号方面的局限性。利用从传统 CD8 T 细胞中学到的经验,我们还讨论了 TCR 信号如何与 MAIT 细胞中的细胞因子信号相结合,从而激发出不同的功能状态。
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来源期刊
Immunological Reviews
Immunological Reviews 医学-免疫学
CiteScore
16.20
自引率
1.10%
发文量
118
审稿时长
4-8 weeks
期刊介绍: Immunological Reviews is a specialized journal that focuses on various aspects of immunological research. It encompasses a wide range of topics, such as clinical immunology, experimental immunology, and investigations related to allergy and the immune system. The journal follows a unique approach where each volume is dedicated solely to a specific area of immunological research. However, collectively, these volumes aim to offer an extensive and up-to-date overview of the latest advancements in basic immunology and their practical implications in clinical settings.
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