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 LegouxPublished 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.
Keyphrases
- induced apoptosis
- single cell
- transcription factor
- cell cycle arrest
- gene expression
- quality improvement
- signaling pathway
- type diabetes
- poor prognosis
- public health
- escherichia coli
- stem cells
- rna seq
- cell proliferation
- dna methylation
- skeletal muscle
- genome wide
- high throughput
- pet ct
- positron emission tomography
- long non coding rna
- pluripotent stem cells
- pi k akt
- binding protein
- heat shock
- heat stress