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

• 成果类型: Article
• 署名作者: Park, Simone L.; Christo, Susan N.; Wells, Alexandria C.; Gandolfo, Luke C.; Zaid, Ali; Alexandre, Yannick O.; Burn, Thomas N.; Schroeder, Jan; Collins, Nicholas; Han, Seong-Ji; Guillaume, Stephane M.; Evrard, Maximilien; Castellucci, Clara; Davies, Brooke; Osman, Maleika; Obers, Andreas; McDonald, Keely M.; Wang, Huimeng; Mueller, Scott N.; Kannourakis, George; Berzins, Stuart P.; Mielke, Lisa A.; Carbone, Francis R.; Kallies, Axel; Speed, Terence P.; Belkaid, Yasmine; Mackay, Laura K.
• 署名单位: University of Melbourne; Peter Doherty Institute; National Institutes of Health (NIH) - USA; University of Melbourne; Walter & Eliza Hall Institute; Federation University Australia; La Trobe University; Olivia Newton-John Cancer Research Institute; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Pennsylvania
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10233
• DOI: 10.1126/science.adi8885
• 发表日期: 2023-12-01
• 页码: 1073-1079
• 关键词: tissue-resident; rm cells; expression; immunity; beta; psoriasis; infection; instruct; PATHWAY; hobit

摘要

Skin-resident CD8(+) T cells include distinct interferon-gamma-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.