Divergent molecular networks program functionally distinct CD8+skin-resident memory T cells
- Authors: Park, Simone , Christo, Susan , Wells, Alexandria , Gandolfo, Luke , Zaid, Ali , Alexandre, Yannick , Burn, Thomas , Schröder, Jan , Collins, Nicholas , Han, Seong-Ji , Guillaume, Stephane , Evrard, Maximilien , Castellucci, Clara , Davies, Brooke , Osman, Maleika , Obers, Andreas , McDonald, Keely , Wang, Huimeng , Mueller, Scott , Kannourakis, George , Berzins, Stuart , Mielke, Lisa , Carbone, Francis , Kallies, Axel , Speed, Terence , Belkaid, Yasmine , MacKay, Laura
- Date: 2023
- Type: Text , Journal article
- Relation: Science Vol. 382, no. 6674 (2023), p. 1073-1079
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- Description: Skin-resident CD8+T cells include distinct interferon-g-producing [tissue-resident memory T type 1 (TRM1)] and interleukin-17 (IL-17)-producing (TRM17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms to establish tissue residence is unknown. In this work, we show that TRM1 and TRM17 cells navigate divergent trajectories to acquire tissue residency in the skin. TRM1 cells depend on a T-bet-Hobit-IL-15 axis, whereas TRM17 cells develop independently of these factors. Instead, c-Maf commands a tissue-resident program in TRM17 cells parallel to that induced by Hobit in TRM1 cells, with an ICOS-c-Maf-IL-7 axis pivotal to TRM17 cell commitment. Accordingly, by targeting this pathway, skin TRM17 cells can be ablated without compromising their TRM1 counterparts. Thus, skin-resident T cells rely on distinct molecular circuitries, which can be exploited to strategically modulate local immunity. © 2023 American Association for the Advancement of Science. All rights reserved.
Sphingosine 1-phosphate receptor 5 (S1PR5) regulates the peripheral retention of tissue-resident lymphocytes
- Authors: Evrard, Maximilien , Wynne-Jones, Erica , Peng, Changwei , Kannourakis, George , Berzins, Stuart
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Experimental Medicine Vol. 219, no. 1 (2021), p.
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- Description: Tissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells. Here, we show that S1PR5 plays a critical role in T cell infiltration and emigration from peripheral organs, as well as being specifically downregulated in TRM cells. Consequentially, TRM cell development was selectively impaired upon ectopic expression of S1pr5, whereas loss of S1pr5 enhanced skin TRM cell formation by promoting peripheral T cell sequestration. Importantly, we found that T-bet and ZEB2 were required for S1pr5 induction and that local TGF-β signaling was necessary to promote coordinated Tbx21, Zeb2, and S1pr5 downregulation. Moreover, S1PR5-mediated control of tissue residency was conserved across innate and adaptive immune compartments. Together, these results identify the T-bet-ZEB2-S1PR5 axis as a previously unappreciated mechanism modulating the generation of tissue-resident lymphocytes. © 2021 Evrard et al.