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

小鼠和人类MAIT细胞转录组的激活和体内演变揭示了组织修复功能

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作者:Timothy S C Hinks ,Emanuele Marchi ,Maisha Jabeen ,Moshe Olshansky ,Ayako Kurioka ,Troi J Pediongco ,Bronwyn S Meehan ,Lyudmila Kostenko ,Stephen J Turner ,Alexandra J Corbett ,Zhenjun Chen ,Paul Klenerman ,James McCluskey

Abstract

Mucosal-associated invariant T (MAIT) cells are MR1-restricted innate-like T cells conserved across mammalian species, including mice and humans. By sequencing RNA from sorted MR1-5-OP-RU tetramer+ cells derived from either human blood or murine lungs, we define the basic transcriptome of an activated MAIT cell in both species and demonstrate how this profile changes during the resolution of infection and during reinfection. We observe strong similarities between MAIT cells in humans and mice. In both species, activation leads to strong expression of pro-inflammatory cytokines and chemokines as well as a strong tissue repair signature, recently described in murine commensal-specific H2-M3-restricted T cells. Transcriptomes of MAIT cells and H2-M3-specific CD8+ T cells displayed the most similarities to invariant natural killer T (iNKT) cells when activated, but to γδ T cells after the resolution of infection. These data define the requirements for and consequences of MAIT cell activation, revealing a tissue repair phenotype expressed upon MAIT cell activation in both species.

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