Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/124802
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Type: Journal article
Title: A divergent transcriptional landscape underpins the development and functional branching of MAIT cells
Author: Koay, H.-.F.
Su, S.
Amann-Zalcenstein, D.
Daley, S.
Comerford, I.
Miosge, L.
Whyte, C.
Konstantinov, I.
d'Udekem, Y.
Baldwin, T.
Hickey, P.
Berzins, S.
Mak, J.
Sontani, Y.
Roots, C.
Sidwell, T.
Kallies, A.
Chen, Z.
Nüssing, S.
Kedzierska, K.
et al.
Citation: ScienceImmunology, 2019; 4(41):eaay6039-1-eaay6039-16
Publisher: Science Immunology; American Association for the Advancement of Science
Issue Date: 2019
ISSN: 2470-9468
2470-9468
Statement of
Responsibility: 
H.-F. Koay, S. Su, D. Amann-Zalcenstein, S.R. Daley, I. Comerford, L. Miosge, C.E. Whyte, I.E. Konstantinov, Y. d’Udekem, T. Baldwin, P.F. Hickey, S.P. Berzins, J.Y.W. Mak, Y. Sontani, C.M. Roots, T. Sidwell, A. Kallies, Z. Chen, S. Nüssing, K. Kedzierska, L.K. Mackay, S.R. McColl, E.K. Deenick, D.P. Fairlie, J. McCluskey, C.C. Goodnow, M.E. Ritchie, G.T. Belz, S.H. Naik, D.G. Pellicci, and D.I. Godfrey
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 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.
Keywords: Animals; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Humans; Mice; Cell Differentiation; Transcription, Genetic; Adult; Signaling Lymphocytic Activation Molecule Family; Mucosal-Associated Invariant T Cells
Rights: © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
RMID: 1000007591
DOI: 10.1126/sciimmunol.aay6039
Grant ID: http://purl.org/au-research/grants/nhmrc/1122277
http://purl.org/au-research/grants/nhmrc/1054925
http://purl.org/au-research/grants/nhmrc/1071916
http://purl.org/au-research/grants/nhmrc/1016953
http://purl.org/au-research/grants/nhmrc/1113904
http://purl.org/au-research/grants/nhmrc/585490
http://purl.org/au-research/grants/nhmrc/1081858
http://purl.org/au-research/grants/nhmrc/1102792
http://purl.org/au-research/grants/nhmrc/1139607
http://purl.org/au-research/grants/nhmrc/1117017
http://purl.org/au-research/grants/nhmrc/1117766
http://purl.org/au-research/grants/nhmrc/1135898
http://purl.org/au-research/grants/arc/CE140100011
Appears in Collections:Microbiology and Immunology publications

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