Journal article
Runx3 drives a CD8 T cell tissue residency program that is absent in CD4 T cells
R Fonseca, TN Burn, LC Gandolfo, S Devi, SL Park, A Obers, M Evrard, SN Christo, FA Buquicchio, CA Lareau, KM McDonald, SK Sandford, NM Zamudio, NG Zanluqui, A Zaid, TP Speed, AT Satpathy, SN Mueller, FR Carbone, LK Mackay
Nature Immunology | Published : 2022
Abstract
Tissue-resident memory T cells (TRM cells) provide rapid and superior control of localized infections. While the transcription factor Runx3 is a critical regulator of CD8+ T cell tissue residency, its expression is repressed in CD4+ T cells. Here, we show that, as a direct consequence of this Runx3-deficiency, CD4+ TRM cells lacked the transforming growth factor (TGF)-β-responsive transcriptional network that underpins the tissue residency of epithelial CD8+ TRM cells. While CD4+ TRM cell formation required Runx1, this, along with the modest expression of Runx3 in CD4+ TRM cells, was insufficient to engage the TGF-β-driven residency program. Ectopic expression of Runx3 in CD4+ T cells incite..
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Awarded by Merck
Funding Acknowledgements
We thank the Flow Cytometry Unit and Bioresources Facility at Peter Doherty Institute (University of Melbourne) for technical assistance. This work was supported by a Howard Hughes Medical Institute and Bill and Melinda Gates International Research Scholarship OPP1175796, National Health and Medical Research Council (NHMRC) AP1113293 to F.RC. and L.K.M. S.L.P. was supported by a NHMRC EL1 Investigator Grant GNT1175626. N.G.Z. was supported by FAPESP (BEPE 2019/12431-2). A.T.S. was supported by the National Institutes of Health (U01CA260852 and UM1HG012076), the Parker Institute for Cancer Immunotherapy and a Pew-Stewart Scholars for Cancer Research Award. L.K.M is a Senior Medical Research Fellow supported by the Sylvia and Charles Viertel Charitable Foundation.