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Cell Rep. 2019 Sep 17;28(12):3249-3262.e5. doi: 10.1016/j.celrep.2019.07.039.

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

Author information

1
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, OX3 9DU, Oxfordshire, UK. Electronic address: timothy.hinks@ndm.ox.ac.uk.
2
Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, OX1 3SY, Oxfordshire, UK.
3
Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, OX3 9DU, Oxfordshire, UK.
4
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Infection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
5
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
6
Infection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
7
Peter Medawar Building for Pathogen Research and Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, OX1 3SY, Oxfordshire, UK; Translational Gastroenterology Unit, Level 5 John Radcliffe Hospital, OX3 9DU, Oxfordshire, UK.

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.

KEYWORDS:

MHC-related protein 1; T cell; activation; human; lung; mouse; mucosal-associated invariant T cell; riboflavin; tissue repair; transcriptome

PMID:
31533045
DOI:
10.1016/j.celrep.2019.07.039
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