美国UT西南医学中心Daolin Tang和Rui Kang共同合作，近期取得重要工作进展。他们研究发现，STING1的核定位与经典信号竞争以激活AHR促进共生和肠道稳态。相关研究成果2023年11月27日在线发表于《免疫学》杂志上。

据介绍，大量研究表明，STING1（又称 STING）蛋白作为一个信号枢纽，协调着免疫和自噬反应，对细胞质中的异位 DNA 起着重要作用。

研究人员报道了STING1在驱动转录因子芳烃受体（AHR）激活以控制肠道微生物群组成和稳态中的核功能。这种功能独立于DNA传感和自噬，并表现出与细胞质环鸟苷单磷酸（GMP）-AMP合成酶（CGAS）-STING1信号传导的竞争性抑制。在结构上，STING1的环状二核苷酸结合结构域与AHR N-末端结构域相互作用。蛋白质组学分析显示，STING1介导的AHR转录激活需要额外的核伴侣，包括阳性和阴性调节蛋白。尽管AHR配体可以挽救野生型小鼠的结肠炎病理和生态失调，但这种保护作用被STING1的突变失活所消除。

总之，这些发现为理解微生物群和免疫系统之间的核分子相互作用建立了一个关键框架。

附：英文原文

Title: Nuclear localization of STING1 competes with canonical signaling to activate AHR for commensal and intestinal homeostasis

Author: Ruoxi Zhang, Chunhua Yu, Herbert J. Zeh, Haichao Wang, Guido Kroemer, Daniel J. Klionsky, Timothy R. Billiar, Rui Kang, Daolin Tang

Issue&Volume: 2023-11-27

Abstract: Extensive studies demonstrate the importance of the STING1 (also known as STING) proteinas a signaling hub that coordinates immune and autophagic responses to ectopic DNAin the cytoplasm. Here, we report a nuclear function of STING1 in driving the activationof the transcription factor aryl hydrocarbon receptor (AHR) to control gut microbiotacomposition and homeostasis. This function was independent of DNA sensing and autophagyand showed competitive inhibition with cytoplasmic cyclic guanosine monophosphate(GMP)-AMP synthase (CGAS)-STING1 signaling. Structurally, the cyclic dinucleotidebinding domain of STING1 interacted with the AHR N-terminal domain. Proteomic analysesrevealed that STING1-mediated transcriptional activation of AHR required additionalnuclear partners, including positive and negative regulatory proteins. Although AHRligands could rescue colitis pathology and dysbiosis in wild-type mice, this protectionwas abrogated by mutational inactivation of STING1. These findings establish a keyframework for understanding the nuclear molecular crosstalk between the microbiotaand the immune system.

DOI: 10.1016/j.immuni.2023.11.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00458-2