Q1 · CROSS-FIELD
Article
Author: Evrard, Maximilien ; Mackay, Laura K ; Davies, Brooke ; Guillaume, Stéphane M ; Zaid, Ali ; Wang, Huimeng ; Speed, Terence P ; McDonald, Keely M ; Mueller, Scott N ; Castellucci, Clara ; Belkaid, Yasmine ; Kallies, Axel ; Burn, Thomas N ; Osman, Maleika ; Alexandre, Yannick O ; Kannourakis, George ; Collins, Nicholas ; Schröder, Jan ; Gandolfo, Luke C ; Carbone, Francis R ; Park, Simone L ; Wells, Alexandria C ; Han, Seong-Ji ; Christo, Susan N ; Berzins, Stuart P ; Mielke, Lisa A ; Obers, Andreas
Skin-resident CD8
+
T cells include distinct interferon-γ–producing [tissue-resident memory T type 1 (T
RM
1)] and interleukin-17 (IL-17)–producing (T
RM
17) 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 T
RM
1 and T
RM
17 cells navigate divergent trajectories to acquire tissue residency in the skin. T
RM
1 cells depend on a T-bet–Hobit–IL-15 axis, whereas T
RM
17 cells develop independently of these factors. Instead, c-Maf commands a tissue-resident program in T
RM
17 cells parallel to that induced by Hobit in T
RM
1 cells, with an ICOS–c-Maf–IL-7 axis pivotal to T
RM
17 cell commitment. Accordingly, by targeting this pathway, skin T
RM
17 cells can be ablated without compromising their T
RM
1 counterparts. Thus, skin-resident T cells rely on distinct molecular circuitries, which can be exploited to strategically modulate local immunity.