MAIT细胞的可塑性使功能适应驱动抗菌免疫保护

IF 17.6 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2024-12-06 DOI:10.1126/sciimmunol.adp9841

Huimeng Wang, Michael N. T. Souter, Marcela de Lima Moreira, Shihan Li, Yuchen Zhou, Adam G. Nelson, Jinhan Yu, Lucy J. Meehan, Bronwyn S. Meehan, Sidonia B. G. Eckle, Hyun Jae Lee, Jan Schröder, Ashraful Haque, Jeffrey Y. W. Mak, David P. Fairlie, James McCluskey, Zhongfang Wang, Zhenjun Chen, Alexandra J. Corbett

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引用次数: 0

摘要

mucal -associated invariant T （MAIT）细胞以其快速效应功能和抗菌免疫保护而闻名。在这里，我们定义了体内产生干扰素-γ (IFN-γ)的MAIT1和产生白细胞介素- 17a （IL-17A）的MAIT17细胞亚群的可塑性。尽管T-bet + MAIT1细胞在所有实验环境中都保持稳定，但在过继性转移或急性军团菌或弗朗西斯菌感染后，RORγt + MAIT17细胞可以在表型和功能上转化为RORγt + T-bet + MAIT1/17和RORγt - T-bet + MAIT1细胞。这种可塑性确保了MAIT17细胞在粘膜组织中产生抗菌MAIT1反应中起主导作用。单细胞转录组学显示，mait17衍生的MAIT1细胞与典型的MAIT1细胞不同，但可以迁移出粘膜组织，在随后的全身性感染中参与全球MAIT1库。人类分泌il - 17a的MAIT细胞也表现出类似的功能可塑性。我们的发现对于理解MAIT细胞在对抗感染中的作用及其在MAIT细胞靶向疫苗中的潜在应用具有广泛的意义。

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MAIT cell plasticity enables functional adaptation that drives antibacterial immune protection

Mucosal-associated invariant T (MAIT) cells are known for their rapid effector functions and antibacterial immune protection. Here, we define the plasticity of interferon-γ (IFN-γ)–producing MAIT1 and interleukin-17A (IL-17A)–producing MAIT17 cell subsets in vivo. Whereas T-bet + MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute Legionella or Francisella infection, RORγt + MAIT17 cells could undergo phenotypic and functional conversion into both RORγt + T-bet + MAIT1/17 and RORγt − T-bet + MAIT1 cells. This plasticity ensured that MAIT17 cells played a dominant role in generating antibacterial MAIT1 responses in mucosal tissues. Single-cell transcriptomics revealed that MAIT17-derived MAIT1 cells were distinct from canonical MAIT1 cells yet could migrate out of mucosal tissues to contribute to the global MAIT1 pool in subsequent systemic infections. Human IL-17A–secreting MAIT cells also showed similar functional plasticity. Our findings have broad implications for understanding the role of MAIT cells in combatting infections and their potential utility in MAIT cell–targeted vaccines.

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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.