研究小组发现转录因子肝白血病因子（HLF）可以指导CD4+ TRM细胞的组织驻留程序和功能。HLF同时上调组织保留受体，下调组织输出受体，并通过诱导Bhlhe40促进促炎CD4+ TRM细胞，这些过程均与染色质可及性的改变有关。在体内，基因缺失Hlf可抑制CD4+ TRM细胞的生成，改善气道组织炎症。从人炎症气道组织中分离的HLF+ CD4+ TRM细胞具有组织驻留特征并表达炎症细胞因子。该课题组得出结论，HLF可能是促炎CD4+ TRM细胞发育和功能的中枢调节因子。
据悉，CD4+组织驻留记忆T （TRM）细胞参与宿主防御和慢性炎症性疾病的发病机制，但指导其分化的分子尚不清楚。
附：英文原文
Title: Hepatic leukemia factor directs tissue residency of proinflammatory memory CD4+ T cells
Author: Masahiro Kiuchi, Masahiro Nemoto, Hiroyuki Yagyu, Ami Aoki, Chiaki Iwamura, Hikaru Sugimoto, Yuki Masuo, Hajime Morita, Shuhe Ma, Yukiko Okuno, Takahisa Hishiya, Kaori Tsuji, Atsushi Sasaki, Kota Kokubo, Kanae Ohishi, Rie Shinmi, Yuri Sonobe, Tomohisa Iinuma, Syuji Yonekura, Tomomasa Yokomizo, Norio Komatsu, Atsushi Onodera, Shinya Okumura, Takashi Ito, Etsuro Hatano, Tatsuaki Tsuruyama, Yosuke Kurashima, Naoko Mato, Takuji Suzuki, Motoko Yagi Kimura, Shinichiro Motohashi, Eiryo Kawakami, Hideki Ueno, Damon J Tumes, Toyoyuki Hanazawa, Toshinori Nakayama, Kiyoshi Hirahara
Issue&Volume: 2025-12-11
Abstract: CD4+ tissue-resident memory T (TRM) cells contribute to host defense and to the pathogenesis of chronic inflammatory diseases, but the molecules that direct their differentiation are unknown. We found that the transcription factor hepatic leukemia factor (HLF) could direct the tissue residency program and function of CD4+ TRM cells. HLF simultaneously up-regulated tissue retention receptors, down-regulated tissue egress receptors, and promoted proinflammatory CD4+ TRM cells by inducing Bhlhe40, and all of these processes were associated with changes in chromatin accessibility. Genetic deletion of Hlf inhibited CD4+ TRM cell generation and ameliorated airway tissue inflammation in vivo. HLF+ CD4+ TRM cells isolated from inflamed airway tissue in humans had a tissue residency signature and expressed inflammatory cytokines. We conclude that HLF may act as a central regulator of proinflammatory CD4+ TRM cell development and function.
DOI: adp0714
Source: https://www.science.org/doi/10.1126/science.adp0714