Journal article

Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity

Susan N Christo, Maximilien Evrard, Simone L Park, Luke C Gandolfo, Thomas N Burn, Raissa Fonseca, Dane M Newman, Yannick O Alexandre, Nicholas Collins, Natasha M Zamudio, Fernando Souza-Fonseca-Guimaraes, Daniel G Pellicci, David Chisanga, Wei Shi, Laurent Bartholin, Gabrielle T Belz, Nicholas D Huntington, Andrew Lucas, Michaela Lucas, Scott N Mueller Show all

NATURE IMMUNOLOGY | NATURE PORTFOLIO | Published : 2021

Abstract

Tissue-resident memory T (TRM) cells are non-recirculating cells that exist throughout the body. Although TRM cells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze TRM cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate TRM cell function, durability and malleability. We find that unequal responsiveness to TGFβ is a major driver of this diversity. Notably, dampened TGFβ signaling results in CD103- TRM cells with increased proliferative potential, enhanced function and reduced longevity compared with ..

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Grants

Awarded by Bill & Melinda Gates International Research Scholarship


Awarded by National Health and Medical Research Council (NHMRC)


Awarded by Priority driven Collaborative Cancer Research Scheme


Awarded by NHMRC


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 & Melinda Gates International Research Scholarship OPP1175796 to L.K.M. and National Health and Medical Research Council (NHMRC) APP1129711 to L.K.M. S.L.P. was supported by a Cancer Council Victoria Postdoctoral Fellowship and an NHMRC Emerging Leadership Investigator Grant. F.S.-F.-G. was supported by a project grant from the NHMRC (no. 1140406), and a grant (no. 1158085) awarded through the Priority driven Collaborative Cancer Research Scheme and funded by Cure Cancer Australia with the assistance of Cancer Australia. L.K.M. is a Senior Medical Research Fellow supported by the Sylvia and Charles Viertel Charitable Foundation.