Activation and In Vivo Evolution of the MAIT Cell Transcriptome in Mice and Humans Reveals Tissue Repair...

Area of Science:

• Immunology
• Cellular and Molecular Immunology

Background:

• Mucosal-associated invariant T (MAIT) cells are MR1-restricted, innate-like T cells found across mammalian species.
• MAIT cells play a conserved role in immune responses.

Purpose of the Study:

• To define the transcriptome of activated MAIT cells in humans and mice.
• To investigate MAIT cell transcriptomic changes during infection resolution and reinfection.

Main Methods:

• RNA sequencing of sorted MR1-5-OP-RU tetramer+ MAIT cells from human blood and murine lungs.
• Comparative transcriptomic analysis between species and conditions.

Main Results:

• MAIT cells in humans and mice exhibit strong similarities in their activated transcriptomes.
• Activation induces pro-inflammatory cytokines, chemokines, and a tissue repair signature.
• MAIT cell transcriptomes resemble iNKT cells upon activation and γδ T cells after infection resolution.

Conclusions:

• MAIT cell activation requires specific conditions and leads to significant functional consequences.
• A conserved tissue repair phenotype is identified upon MAIT cell activation in both humans and mice.