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Article Dans Une Revue Journal of Experimental Medicine Année : 2024

A conserved transcriptional program for MAIT cells across mammalian evolution

Helene Bugaut
Yara El Morr
Martin Mestdagh
Aurelie Darbois
Rafael A. Paiva
Marion Salou
Laetitia Perrin
Anastasia Du Halgouet
Linda Bilonda Mutala
Anne‐laure Le Gac
Manon Arnaud
Ahmed El Marjou
Valdone Maciulyte
James M. A. Turner
Olivier Lantz

Résumé

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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Origine : Publication financée par une institution
Licence : CC BY NC SA - Paternité - Pas d'utilisation commerciale - Partage selon les Conditions Initiales

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hal-04386054 , version 1 (15-01-2024)

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Paternité - Pas d'utilisation commerciale - Partage selon les Conditions Initiales

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Helene Bugaut, Yara El Morr, Martin Mestdagh, Aurelie Darbois, Rafael A. Paiva, et al.. A conserved transcriptional program for MAIT cells across mammalian evolution. Journal of Experimental Medicine, 2024, Journal of Experimental Medicine, 221 (2), pp.e20231487. ⟨10.1084/jem.20231487⟩. ⟨hal-04386054⟩
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