Activation and In Vivo Evolution of the MAIT Cell Transcriptome in Mice and Humans Reveals Tissue Repair Functionality
Timothy SC 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
CELL REPORTS | CELL PRESS | Published : 2019
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-re..View full abstract
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Awarded by Wellcome Trust
Awarded by National Health and Medical Research Council of Australia (NHMRC)
This work was funded by grants to T.S.C.H. from the Wellcome Trust (104553/z/14/z and 211050/Z/18/z). The work was supported by the National Health and Medical Research Council of Australia (NHMRC) program grants 1113293, 1071916, 1016629, and 606788 and project grant 1120467. A. J. C. is supported by an ARC Future Fellowship. S.B.G. is supported by an ARC DECRA Fellowship. P.K. was supported by an NIHR Senior Fellowship, Oxford Martin School, and the Wellcome Trust (WT109965MA). This work benefitted from data assembled by the ImmGen consortium (Heng et al., 2008). We are grateful to Dr. Brendan Russ and Dr. Linda Wakim for assistance and suggestions for experimental design; Dr. Ama Essilfie, Prof. Richard Strugnell, Frances Oppodisam, Jennifer Davies, Prof. Roy Robbins-Browne, Prof. Kenneth Beagley, and Dr. Hayley Newton for bacterial strains; Prof. David Jackson for Pam2Cys; Dr. Jeffrey Mak for MR1 ligands; Dr. Vanta Jameson, Mr. Josh Kie at the Flow Cytometry Facilities at the Melbourne Brain Centre and the Peter Doherty Institute; and Kym Pham and Karey Cheong at the Melbourne Translational Genomic Platform.