研究人员表示，皮肤驻留的CD8+ T细胞包括不同的干扰素-γ生成亚群[组织驻留记忆T1型（TRM1）]和白细胞介素-17（IL-17）生成亚群（TRM17），它们对免疫反应有不同的贡献。然而，这些群体是否使用共同的机制来建立组织驻留尚不清楚。
研究人员发现TRM1和TRM17细胞以不同的轨迹在皮肤中获得组织驻留。TRM1细胞依赖于T-bet-Hobit-IL-15轴，而TRM17细胞的发育则独立于这些因素。相反，c-Maf在TRM17细胞中指挥组织驻留程序，与Hobit在TRM1细胞中诱导的程序平行，ICOS-c-Maf-IL-7轴对TRM17细胞的确立至关重要。因此，通过靶向这一途径，可以去除皮肤TRM17细胞，而不影响其对应的TRM1细胞。因此，皮肤驻留的T细胞依赖于不同的分子回路，可以利用这些回路策略性地调节局部免疫。
附：英文原文
Title: Divergent molecular networks program functionally distinct CD8+ skin-resident memory T cells
Author: Simone L. Park, Susan N. Christo, Alexandria C. Wells, Luke C. Gandolfo, Ali Zaid, Yannick O. Alexandre, Thomas N. Burn, Jan Schrder, Nicholas Collins, Seong-Ji Han, Stéphane M. Guillaume, 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
Issue&Volume: 2023-12-01
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.
DOI: adi8885
Source: https://www.science.org/doi/10.1126/science.adi8885