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

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dc.contributor.authorKoay, H.-F.
dc.contributor.authorSu, S.
dc.contributor.authorAmann-Zalcenstein, D.
dc.contributor.authorDaley, S.R.
dc.contributor.authorComerford, I.
dc.contributor.authorMiosge, L.
dc.contributor.authorWhyte, C.E.
dc.contributor.authorKonstantinov, I.E.
dc.contributor.authord'Udekem, Y.
dc.contributor.authorBaldwin, T.
dc.contributor.authorHickey, P.F.
dc.contributor.authorBerzins, S.P.
dc.contributor.authorMak, J.Y.W.
dc.contributor.authorSontani, Y.
dc.contributor.authorRoots, C.M.
dc.contributor.authorSidwell, T.
dc.contributor.authorKallies, A.
dc.contributor.authorChen, Z.
dc.contributor.authorNüssing, S.
dc.contributor.authorKedzierska, K.
dc.contributor.authoret al.
dc.date.issued2019
dc.description.abstractMR1-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.
dc.description.statementofresponsibilityH.-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
dc.identifier.citationScience Immunology, 2019; 4(41):eaay6039-1-eaay6039-16
dc.identifier.doi10.1126/sciimmunol.aay6039
dc.identifier.issn2470-9468
dc.identifier.issn2470-9468
dc.identifier.orcidMcColl, S.R. [0000-0003-0949-4660]
dc.identifier.urihttp://hdl.handle.net/2440/124802
dc.language.isoen
dc.publisherScience Immunology; American Association for the Advancement of Science
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1122277
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1054925
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1071916
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1016953
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1113904
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/585490
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1081858
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1102792
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1139607
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1117017
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1117766
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1135898
dc.relation.granthttp://purl.org/au-research/grants/arc/CE140100011
dc.rights© 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
dc.source.urihttps://doi.org/10.1126/sciimmunol.aay6039
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectMice, Inbred C57BL
dc.subjectMice, Transgenic
dc.subjectHumans
dc.subjectMice
dc.subjectCell Differentiation
dc.subjectTranscription, Genetic
dc.subjectAdult
dc.subjectSignaling Lymphocytic Activation Molecule Family
dc.subjectMucosal-Associated Invariant T Cells
dc.titleA divergent transcriptional landscape underpins the development and functional branching of MAIT cells
dc.typeJournal article
pubs.publication-statusPublished

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