Divergent molecular networks program functionally distinct CD8+skin-resident memory T cells

• DOI: 10.1126/science.adi8885
• Publication Date: 2023-11-30T19:01:18Z
• Authors: Simone L. Park; Susan N. Christo; Alexandria C. Wells; Luke C. Gandolfo; Ali Zaid; Yannick O. Alexandre; Thomas N. Burn; Jan Schröder; Nicholas Collins; Seong-Ji Han; Stéphane M. Guill...; Maximilien Evrard; Clara Castellucci; Brooke Davies; Maleika Osman; Andreas Obers; Keely M. McDonald; Huimeng Wang; Scott N. Mueller; George Kannourakis; Stuart P. Berzins; Lisa A. Mielke; Francis R. Carbone; Axel Kallies; Terence P. Speed; Yasmine Belkaid; Laura K. Mackay
• Keywords: Interleukin 3

Skin-resident CD8+ T cells include distinct interferon-γ-producing [tissue-resident memory type 1 (TRM1)] and interleukin-17 (IL-17)-producing (TRM17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms establish tissue residence is unknown. In this work, we show TRM1 TRM17 navigate divergent trajectories acquire residency in the skin. depend on a T-bet-Hobit-IL-15 axis, whereas develop independently of factors. Instead, c-Maf commands tissue-resident program parallel induced by Hobit cells, with an ICOS-c-Maf-IL-7 axis pivotal cell commitment. Accordingly, targeting pathway, skin can be ablated without compromising their counterparts. Thus, skin-resident rely molecular circuitries, which exploited strategically modulate local immunity.