A conserved transcriptional program for MAIT cells across mammalian evolution

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Bugaut, Helene | El Morr, Yara | Mestdagh, Martin | Darbois, Aurelie | A. Paiva, Rafael | Salou, Marion | Perrin, Laetitia | Furstenheim, Mariela | Du Halgouet, Anastasia | Mutala, Linda, Bilonda | Le Gac, Anne‐laure | Arnaud, Manon | El Marjou, Ahmed | Guerin, Coralie | Chaiyasitdhi, Atitheb | Piquet, Julie | Smadja, David M | Cieslak, Agata | Ryffel, Bernhard | Maciulyte, Valdone | Turner, James M. A. | Bernardeau, Karine | Montagutelli, Xavier | Lantz, Olivier | Legoux, Francois

Edité par CCSD ; Rockefeller University Press -

International audience. 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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