A Conserved Transcriptional Program for MAIT Cells Across Mammalian Evolution

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2023 Dec 20

PMID 38117256

Authors

Helene Bugaut

Yara El Morr

Martin Mestdagh

Aurelie Darbois

Rafael A Paiva

Marion Salou

Laetitia Perrin

Mariela Furstenheim

Anastasia du Halgouet

Linda Bilonda-Mutala

Anne-Laure Le Gac

Manon Arnaud

Ahmed El Marjou

Coralie Guerin

Atitheb Chaiyasitdhi

Julie Piquet

David M Smadja

Agata Cieslak

Bernhard Ryffel

Valdone Maciulyte

James M A Turner

Karine Bernardeau

Xavier Montagutelli

Olivier Lantz

Francois Legoux

Affiliations

Soon will be listed here.

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.

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