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ORIGINAL RESEARCH article

Front. Immunol.
Sec. T Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1504806

The effector function of mucosal associated invariant T cells alters with aging and is regulated by RORγt

Provisionally accepted
Zhi Yang Zhi Yang 1Banxin Luo Banxin Luo 2*Minhuan Li Minhuan Li 3*Ziyun He Ziyun He 4Chuanfu Ren Chuanfu Ren 1*Xin Chen Xin Chen 2*Xing Kang Xing Kang 3*Hong Chen Hong Chen 3*En Xu En Xu 3Wenxian Guan Wenxian Guan 3*Xuefeng Xia Xuefeng Xia 3*
  • 1 Nanjing Medical University, Nanjing, China
  • 2 Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
  • 3 Nanjing University, Nanjing, Jiangsu Province, China
  • 4 Wuhan University, Wuhan, Hubei Province, China

The final, formatted version of the article will be published soon.

    Mucosal-associated invariant T cells (MAIT cells), the predominant innate-like T cells in humans, exhibit diverse gene expression profiles and functional capabilities. The factors influencing the transcriptomes and effector functions of MAIT cells at mucosal barriers remain yet largely unclear.In this study, utilizing single-cell RNA sequencing (scRNA-seq) and functional assays, we show that the transcriptomes and functional capabilities of intestinal MAIT cells shifted from MAIT17 to MAIT1 profiles with aging in mouse models, with variable changes in the production of cytotoxic molecules. Further scRNA-seq analysis revealed that human intestinal MAIT cells segregate into MAIT1 and MAIT17 subsets, exhibiting similar gene expression patterns of effector molecules resembling the changes of MAIT cells in aged mouse models. The transcription factor RORγt was expressed in both MAIT1 and MAIT17 cells, where it repressed IFNγ production while promoting IL17 expression. Reduced expression of RORC and Il17A correlated with worse survival in colorectal cancers. Together, our results suggest that aging triggers a switch between MAIT1 and MAIT17 cells and that factors influencing MAIT cell activities might correlate with disease prognosis.

    Keywords: Mucosal-associated invariant T cells (MAIT), MAIT1, MAIT17, Aging, ScRNA-seq

    Received: 01 Oct 2024; Accepted: 01 Nov 2024.

    Copyright: © 2024 Yang, Luo, Li, He, Ren, Chen, Kang, Chen, Xu, Guan and Xia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Banxin Luo, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
    Minhuan Li, Nanjing University, Nanjing, 210093, Jiangsu Province, China
    Chuanfu Ren, Nanjing Medical University, Nanjing, China
    Xin Chen, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
    Xing Kang, Nanjing University, Nanjing, 210093, Jiangsu Province, China
    Hong Chen, Nanjing University, Nanjing, 210093, Jiangsu Province, China
    Wenxian Guan, Nanjing University, Nanjing, 210093, Jiangsu Province, China
    Xuefeng Xia, Nanjing University, Nanjing, 210093, Jiangsu Province, China

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