A divergent transcriptional landscape underpins the development and functional branching of MAIT cells

HF Koay; S Su; D Amann-Zalcenstein; SR Daley; I Comerford; L Miosge; CE Whyte; IE Konstantinov; Y D'Udekem; T Baldwin; PF Hickey; SP Berzins; JYW Mak; Y Sontani; CM Roots; T Sidwell; A Kallies; Z Chen; S Nüssing; K Kedzierska; LK Mackay; SR McColl; EK Deenick; DP Fairlie; J McCluskey; CC Goodnow; ME Ritchie; GT Belz; SH Naik; DG Pellicci; DI Godfrey

Journal article

A divergent transcriptional landscape underpins the development and functional branching of MAIT cells

HF Koay, S Su, D Amann-Zalcenstein, SR Daley, I Comerford, L Miosge, CE Whyte, IE Konstantinov, Y D'Udekem, T Baldwin, PF Hickey, SP Berzins, JYW Mak, Y Sontani, CM Roots, T Sidwell, A Kallies, Z Chen, S Nüssing, K Kedzierska Show all

Science Immunology | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2019

DOI: 10.1126/sciimmunol.aay6039

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Abstract

MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymically through a three-stage process, but the events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing-based transcriptomic analysis in mice and humans, we studied the changing transcriptional landscape that accompanies transition through each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic activation molecule) family members, chemokine receptors, and transcription factors. We also demonstrate that stage 3 "mature" MAIT cells comprise distinct subpopulations inc..

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University of Melbourne Researchers

Fern Koay Author

Daniela Amann-Zalcenstein Author

Igor Konstantinov Author

Yves D'Udekem D'Acoz Author

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Grants

Awarded by National Institutes of Health

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (NHMRC): 1083942, 1113293, and 1140126 to D.I.G.; NHMRC 1122277 and 1054925 to G.T.B.; NHMRC 1071916 to K.K.; and NHMRC 1016953, 1113904, 585490, and 1081858 and the National Institutes of Health (U19-AI100627) to C.C.G. H.-F.K. is supported by an NHMRC ECF Fellowship (1160333); D.I.G., H.-F.K., D.P.F., and D.G.P. are also supported by the Australian Research Council CE140100011. D.G.P. is supported by a CSL Centenary Fellowship; K.K. is supported by an NHMRC Senior Research Fellowship (1102792); A.K. is supported by an NHMRC Fellowship (1139607); and D.P.F., D.I.G., and G.T.B. are supported by NHMRC Senior Principal Research Fellowships (1117017, 1117766, and 1135898, respectively). This study was made possible through the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme.