Divergent molecular networks program functionally distinct CD8+ skin-resident memory T cells.
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| Title: | Divergent molecular networks program functionally distinct CD8+ skin-resident memory T cells. |
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| Authors: | Park, Simone L., Christo, Susan N., Wells, Alexandria C., Gandolfo, Luke C., Zaid, Ali, Alexandre, Yannick O., Burn, Thomas N., Schröder, Jan, Collins, Nicholas, Seong-Ji Han, Guillaume, Stéphane M., Evrard, Maximilien, Castellucci, Clara, Davies, Brooke, Osman, Maleika, Obers, Andreas, McDonald, Keely M., Huimeng Wang, Mueller, Scott N., Kannourakis, George |
| Source: | Science (pre-March 2025). 12/1/2023, Vol. 382 Issue 6674, p1073-1079. 7p. 4 Diagrams. |
| Subjects: | Immunologic memory, CD8 antigen, Cell determination, T cells, Immune response, Interleukin-17 |
| Abstract: | Skin-resident CD8+ T cells include distinct interferon-γ–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. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Skin-resident CD8+ T cells include distinct interferon-γ–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. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.adi8885 |
