效应器
细胞毒性T细胞
细胞生物学
生物
化学
遗传学
体外
作者
Huafeng Zhang,Zhonghan Yang,Wei Yuan,Jincheng Liu,Xiao Luo,Qian Zhou,Yonggang Li,Jie Chen,Yabo Zhou,Jiadi Lv,Nannan Zhou,Jingwei Ma,Ke Tang,Bo Huang
标识
DOI:10.1073/pnas.2317658121
摘要
Identification of mechanisms that program early effector T cells to either terminal effector T (T eff ) or memory T (T m ) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early T eff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8 + T eff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8 + T cells up-regulate HIF-1α to compete with AhR for HIF-1β, leading to the loss of AhR activity in HIF-1α high short-lived effector cells, but sustained in HIF-1α low memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8 + MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how T eff cells are regulated to differentiate into memory cells.
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