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https://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.R. Comerford, I. Miosge, L. Whyte, C.E. Konstantinov, I.E. d'Udekem, Y. Baldwin, T. Hickey, P.F. Berzins, S.P. Mak, J.Y.W. Sontani, Y. Roots, C.M. Sidwell, T. Kallies, A. Chen, Z. Nüssing, S. Kedzierska, K. et al. |
Citation: | Science Immunology, 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 |
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 |
Published version: | http://dx.doi.org/10.1126/sciimmunol.aay6039 |
Appears in Collections: | Aurora harvest 4 Microbiology and Immunology publications |
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