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Cbf-β is required for the development, differentiation, and function of murine mucosal-associated invariant T cells

Cellular & Molecular Immunology volume 19, pages 1314–1316 (2022)Cite this article

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Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved subset of T cells that respond to microbial threats via semi-invariant T cell receptor (TCR)-mediated recognition of microbial riboflavin-derivative antigens presented by MHC class I-related (MR1) molecules [1]. MAIT cells mediate functions that link innate and acquired immunity in a broad spectrum of diseases, including infection, cancer, allergy, and autoimmunity [2]. MAIT cells are abundant in human nonmucosal tissues, where they account for up to 10% of blood T cells and 45% of liver T cells, but are much less abundant in mice [3].

Recently, the availability of MR1-loaded tetramers has allowed the study of MAIT cells in mice [3, 4] and facilitated the mapping of murine thymic MAIT cell development, revealing that MAIT cells originate from CD4+CD8+ precursors and undergo maturation through the following three stages: stage 1, CD24+CD44– cells; stage 2, CD24–CD44– cells; and stage 3, CD24–CD44+ cells [4]. Stage 3 MAIT cells further differentiate into the following effector lineages in the thymus: IFN-γ–secreting T-bet+ MAIT1 cells and IL-17–secreting RORγt+ MAIT17 cells [5]. The specific cytokines produced by MAIT1 and MAIT17 cells and the relative frequencies of these cell types have a major impact on the pathogenesis of cancer and autoimmune diseases. Therefore, to develop MAIT cell-based therapies, it is crucial to identify novel targets for regulating MAIT cell development and differentiation. Although transcription factors such as PLZF, SATB1, miR-181a/b-1, miR-155, Drosha, and the adapter molecule SAP have been shown to regulate MAIT cell development and differentiation [6, 7], a significant gap in our knowledge of MAIT cell regulation remains.

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Acknowledgements

We would like to thank the NIH tetramer core for providing tetramers, Peter Dimitrion, Nirmal Parajuli for performing tamoxifen injections, and Karla Passalacqua for assistance with editing the manuscript. JST acknowledges AN for support of this work.

Funding

Henry Ford Immunology Research Program (T71016 to QSM, T71017 to LZ).

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Author notes

  1. These authors contributed equally: Tingting Liu, Jugmohit S. Toor.

Authors and Affiliations

  1. Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI, USA

    Tingting Liu, Jugmohit S. Toor, Kalpana Subedi, Jie Wang, Qijun Yi, Ian Loveless, Li Zhou & Qing-Sheng Mi

  2. Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, USA

    Tingting Liu, Jugmohit S. Toor, Kalpana Subedi, Jie Wang, Qijun Yi, Ian Loveless, Li Zhou & Qing-Sheng Mi

  3. Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250022, China

    Tingting Liu

  4. Wayne State University School of Medicine, Detroit, MI, USA

    Jugmohit S. Toor, Li Zhou & Qing-Sheng Mi

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Contributions

QSM and LZ conceived and designed the project. TL, JST, KS, QY, and JW harvested and processed mouse tissues. TL and JST designed and performed the flow cytometry experiments. JST, TL, and IL analyzed the data. JST, TL, and QSM wrote the manuscript with feedback from all authors.

Corresponding authors

Correspondence to Li Zhou or Qing-Sheng Mi.

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The authors declare no competing interests.

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Liu, T., Toor, J.S., Subedi, K. et al. Cbf-β is required for the development, differentiation, and function of murine mucosal-associated invariant T cells. Cell Mol Immunol 19, 1314–1316 (2022). https://doi.org/10.1038/s41423-022-00920-y

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