학술논문
A conserved transcriptional program for MAIT cells across mammalian evolution
Document Type
Article
Author
Bugaut, Hélène; El Morr, Yara; Mestdagh, Martin; Darbois, Aurélie; Paiva, Rafael A.; Salou, Marion; Perrin, Laetitia; Fürstenheim, Mariela; du Halgouet, Anastasia; Bilonda-Mutala, Linda; 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, François
Source
The Journal of Experimental Medicine; February 2024, Vol. 221 Issue: 2 pe20231487-e20231487, 1p
Subject
Language
ISSN
00221007; 15409538
Abstract
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.