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

Autor:	Koay HF; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3000, Australia., Su S; Epigenetics and Development Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.; Single Cell Open Research Endeavour (SCORE), Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia., Amann-Zalcenstein D; Single Cell Open Research Endeavour (SCORE), Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.; Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Daley SR; Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia., Comerford I; Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia., Miosge L; Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia., Whyte CE; Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia., Konstantinov IE; Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.; Melbourne Children's Centre for Cardiovascular Genomics and Regenerative Medicine, Murdoch Children's Research Institute, Victoria 3052, Australia.; Murdoch Children's Research Institute, Victoria 3052, Australia., d'Udekem Y; Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia.; Melbourne Children's Centre for Cardiovascular Genomics and Regenerative Medicine, Murdoch Children's Research Institute, Victoria 3052, Australia.; Murdoch Children's Research Institute, Victoria 3052, Australia., Baldwin T; Single Cell Open Research Endeavour (SCORE), Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia.; Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia., Hickey PF; Single Cell Open Research Endeavour (SCORE), Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia., Berzins SP; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.; Federation University Australia, Ballarat, Victoria 3350, Australia.; Fiona Elsey Cancer Research Institute, Ballarat, Victoria 3350, Australia., Mak JYW; Division of Chemistry and Structural Biology, and Centre for Inflammation and Disease Research, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Queensland, Brisbane, Queensland 4072, Australia., Sontani Y; Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia., Roots CM; Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia., Sidwell T; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Kallies A; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Chen Z; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Nüssing S; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Kedzierska K; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Mackay LK; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3000, Australia., McColl SR; Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia., Deenick EK; Garvan Institute of Medical Research, Sydney, Australia.; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales (UNSW), Sydney, Australia., Fairlie DP; Division of Chemistry and Structural Biology, and Centre for Inflammation and Disease Research, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Queensland, Brisbane, Queensland 4072, Australia., McCluskey J; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia., Goodnow CC; Garvan Institute of Medical Research, Sydney, Australia.; UNSW Cellular Genomics Futures Institute, UNSW, Sydney, Australia., Ritchie ME; Epigenetics and Development Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Belz GT; Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Naik SH; Single Cell Open Research Endeavour (SCORE), Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.; Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.; Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3010, Australia., Pellicci DG; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia. godfrey@unimelb.edu.au dan.pellicci@mcri.edu.au.; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3000, Australia.; Murdoch Children's Research Institute, Victoria 3052, Australia., Godfrey DI; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia. godfrey@unimelb.edu.au dan.pellicci@mcri.edu.au.; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria 3000, Australia.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2019 Nov 22; Vol. 4 (41).
DOI:	10.1126/sciimmunol.aay6039
Abstrakt:	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 including newly arrived transitional stage 3 cells, interferon-γ-producing MAIT1 cells and interleukin-17-producing MAIT17 cells. Moreover, the validity and importance of several transcripts detected in this study are directly demonstrated using specific mutant mice. For example, MAIT cell intrathymic maturation was found to be halted in SLAM-associated protein (SAP)-deficient and CXCR6-deficient mouse models, providing clear evidence for their role in modulating MAIT cell development. These data underpin a model that maps the changing transcriptional landscape and identifies key factors that regulate the process of MAIT cell differentiation, with many parallels between mice and humans. (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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