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A conserved transcriptional program for MAIT cells across mammalian evolution.

Hélène BugautYara El MorrMartin MestdaghAurelie Darbois-DelahousseRafael A PaivaMarion SalouLaetitia PerrinMariela FürstenheimAnastasia du HalgouetLinda Bilonda MutalaAnne-Laure Le GacManon ArnaudAhmed El MarjouCoralie L GuerinAtitheb ChaiyasitdhiJulie PiquetDavid M SmadjaAgata CieslakBernhard RyffelValdone MaciulyteJames M A TurnerKarine BernardeauXavier MontagutelliOlivier LantzFrancois Legoux
Published in: The Journal of experimental medicine (2023)
Mucosal-associated invariant T (MAIT) cells harbor evolutionarily conserved TCRs, suggesting important functions. As human and mouse MAIT functional programs appear distinct, the evolutionarily conserved MAIT functional features remain unidentified. Using species-specific tetramers coupled to single-cell RNA sequencing, we characterized MAIT cell development in six species spanning 110 million years of evolution. Cross-species analyses revealed conserved transcriptional events underlying MAIT cell maturation, marked by ZBTB16 induction in all species. MAIT cells in human, sheep, cattle, and opossum acquired a shared type-1/17 transcriptional program, reflecting ancestral features. This program was also acquired by human iNKT cells, indicating common differentiation for innate-like T cells. Distinct type-1 and type-17 MAIT subsets developed in rodents, including pet mice and genetically diverse mouse strains. However, MAIT cells further matured in mouse intestines to acquire a remarkably conserved program characterized by concomitant expression of type-1, type-17, cytotoxicity, and tissue-repair genes. Altogether, the study provides a unifying view of the transcriptional features of innate-like T cells across evolution.
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