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. MuellerWilliam R. Heath, Florent Ginhoux, Terence P. Speed, Francis R. Carbone, Axel Kallies, Laura K. Mackay

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

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 their TGFβ-responsive CD103+ TRM counterparts. Furthermore, whereas CD103 TRM cells readily modified their phenotype upon relocation, CD103+ TRM cells were comparatively resistant to transdifferentiation. Thus, despite common requirements for TRM cell development, tissue adaptation of these cells confers discrete functional properties such that TRM cells exist along a spectrum of differentiation potential that is governed by their local tissue microenvironment.

Original languageEnglish
Pages (from-to)1140-1151
Number of pages12
JournalNature Immunology
Volume22
Issue number9
DOIs
Publication statusPublished - Sept 2021

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