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, K. 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 Y. Kimura, Shinichiro Motohashi, Eiryo Kawakami, Hideki Ueno, Damon J. Tumes, Toyoyuki Hanazawa, Toshinori Nakayama, Kiyoshi Hirahara
CD4 + tissue-resident memory T (T RM ) 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 + T RM cells. HLF simultaneously up-regulated tissue retention receptors, down-regulated tissue egress receptors, and promoted proinflammatory CD4 + T RM cells by inducing Bhlhe40 , and all of these processes were associated with changes in chromatin accessibility. Genetic deletion of Hlf inhibited CD4 + T RM cell generation and ameliorated airway tissue inflammation in vivo. HLF + CD4 + T RM 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 + T RM cell development and function.