Single-cell transcriptional profiling reveals signatures of helper, effector, and regulatory MAIT cells during homeostasis and activation Journal Article
| Authors: | Vorkas, C. K.; Krishna, C.; Li, K.; Aubé, J.; Fitzgerald, D. W.; Mazutis, L.; Leslie, C. S.; Glickman, M. S. |
| Article Title: | Single-cell transcriptional profiling reveals signatures of helper, effector, and regulatory MAIT cells during homeostasis and activation |
| Abstract: | Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that recognize microbial vitamin B metabolites and have emerging roles in infectious disease, autoimmunity, and cancer. Although MAIT cells are identified by a semi-invariant TCR, their phenotypic and functional heterogeneity is not well understood. Here we present an integrated single cell transcriptomic analysis of over 76,000 human MAIT cells during early and prolonged Ag-specific activation with the MR1 ligand 5-OP-RU and nonspecific TCR stimulation. We show that MAIT cells span a broad range of homeostatic, effector, helper, tissue-infiltrating, regulatory, and exhausted phenotypes, with distinct gene expression programs associated with CD4+ or CD8+ coexpression. During early activation, MAIT cells rapidly adopt a cytotoxic phenotype characterized by high expression of GZMB, IFNG and TNF In contrast, prolonged stimulation induces heterogeneous states defined by proliferation, cytotoxicity, immune modulation, and exhaustion. We further demonstrate a FOXP3 expressing MAIT cell subset that phenotypically resembles conventional regulatory T cells. Moreover, scRNAseq-defined MAIT cell subpopulations were also detected in individuals recently exposed to Mycobacterium tuberculosis, confirming their presence during human infection. To our knowledge, our study provides the first comprehensive atlas of human MAIT cells in activation conditions and defines substantial functional heterogeneity, suggesting complex roles in health and disease. Copyright © 2022 by The American Association of Immunologists, Inc. |
| Keywords: | genetics; cd8+ t lymphocyte; cell proliferation; cd8-positive t-lymphocytes; forkhead transcription factors; cytology; metabolism; cells, cultured; gene expression profiling; immunology; lymphocyte activation; mycobacterium tuberculosis; tumor necrosis factor-alpha; gamma interferon; cell culture; receptors, antigen, t-cell; cd4+ t lymphocyte; cd4-positive t-lymphocytes; interferon-gamma; homeostasis; forkhead transcription factor; transcriptome; lymphocyte antigen receptor; foxp3 protein, mouse; tumor necrosis factor; granzymes; single cell analysis; single-cell analysis; uracil; granzyme; humans; human; gzmb protein, mouse; ifng protein, mouse; mucosal-associated invariant t cell; 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil; ribitol; tnf protein, mouse; mucosal-associated invariant t cells |
| Journal Title: | Journal of Immunology |
| Volume: | 208 |
| Issue: | 5 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2022-03-01 |
| Start Page: | 1042 |
| End Page: | 1056 |
| Language: | English |
| DOI: | 10.4049/jimmunol.2100522 |
| PUBMED: | 35149530 |
| PROVIDER: | scopus |
| PMCID: | PMC9012082 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2022 -- Source: Scopus |
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