Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity
- Christo, SN; Evrard, M; Park, SL; Gandolfo, LC; Burn, TN; Fonseca, R; Newman, DM; Alexandre, YO; Collins, N; Zamudio, NM; Souza-Fonseca-Guimaraes, F; Pellicci, DG; Chisanga, D; Shi, W; Bartholin, L; Belz, GT; Huntington, ND; Lucas, A; Lucas, M; Mueller, SN; Heath, WR; Ginhoux, F; Speed, TP; Carbone, FR; Kallies, A; Mackay, LK;
Publication Year 2021-09, Volume 22, Issue #9, Page 1140-1151
- Journal Title
- Nature Immunology
- Tissue-resident memory T (T(RM)) cells are non-recirculating cells that exist throughout the body. Although T(RM) 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 T(RM) cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate T(RM) 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(-) T(RM) cells with increased proliferative potential, enhanced function and reduced longevity compared with their TGFβ-responsive CD103(+) T(RM) counterparts. Furthermore, whereas CD103(-) T(RM) cells readily modified their phenotype upon relocation, CD103(+) T(RM) cells were comparatively resistant to transdifferentiation. Thus, despite common requirements for T(RM) cell development, tissue adaptation of these cells confers discrete functional properties such that T(RM) cells exist along a spectrum of differentiation potential that is governed by their local tissue microenvironment.
- WEHI Research Division(s)
- PubMed ID
- Publisher's Version
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Creation Date: 2021-09-17 11:23:07Last Modified: 2021-09-17 11:32:15