Transcriptomes and metabolism define mouse and human MAIT cell populations

Shilpi Chandra, Gabriel Ascui, Thomas Riffelmacher, Ashu Chawla, Ciro Ramírez-Suástegui, Viankail C. Castelan, Gregory Seumois, Hayley Simon, Mallory P. Murray, Goo Young Seo, Ashmitaa L.R. Premlal, Benjamin Schmiedel, Greet Verstichel, Yingcong Li, Chia Hao Lin, Jason Greenbaum, John Lamberti, Raghav Murthy, John Nigro, Hilde CheroutreChristian H. Ottensmeier, Stephen M. Hedrick, Li Fan Lu, Pandurangan Vijayanand, Mitchell Kronenberg

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Mucosal-associated invariant T (MAIT) cells are a subset of T lymphocytes that respond to microbial metabolites. We defined MAIT cell populations in different organs and characterized the developmental pathway of mouse and human MAIT cells in the thymus using single-cell RNA sequencing and phenotypic and metabolic analyses. We showed that the predominant mouse subset, which produced IL-17 (MAIT17), and the subset that produced IFN-γ (MAIT1) had not only greatly different transcriptomes but also different metabolic states. MAIT17 cells in different organs exhibited increased lipid uptake, lipid storage, and mitochondrial potential compared with MAIT1 cells. All these properties were similar in the thymus and likely acquired there. Human MAIT cells in lung and blood were more homogeneous but still differed between tissues. Human MAIT cells had increased fatty acid uptake and lipid storage in blood and lung, similar to human CD8 T resident memory cells, but unlike mouse MAIT17 cells, they lacked increased mitochondrial potential. Although mouse and human MAIT cell transcriptomes showed similarities for immature cells in the thymus, they diverged more strikingly in the periphery. Analysis of pet store mice demonstrated decreased lung MAIT17 cells in these so-called “dirty” mice, indicative of an environmental influence on MAIT cell subsets and function.

Original languageEnglish
Article numbereabn8531
JournalScience immunology
Volume8
Issue number89
DOIs
StatePublished - 2023

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