STING controls nociception via type I interferon signalling in sensory neurons.
STING controls nociception via type I interferon signalling in sensory neurons.
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DOI：
10.1038/s41586-020-03151-1
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发表时间：
2021-03
期刊：
影响因子：
64.8
通讯作者：
Ji RR
中科院分区：
文献类型：
--
作者：
Donnelly CR;Jiang C;Andriessen AS;Wang K;Wang Z;Ding H;Zhao J;Luo X;Lee MS;Lei YL;Maixner W;Ko MC;Ji RR
先天免疫调节剂STING是自身和病原体来源的DNA的关键传感器，导致I型干扰素（IFN-I）和其他细胞因子的诱导，其促进免疫细胞介导的病原体和肿瘤细胞的根除。STING也已成为抗肿瘤免疫的强大驱动力，导致STING激活剂和小分子激动剂被开发为癌症免疫治疗佐剂。由外周伤害感受性感觉神经元（伤害感受器）传递的疼痛也通过提醒生物体存在潜在的破坏性刺激（包括病原体和癌细胞）来帮助宿主防御。在这里，我们证明了STING是通过外周伤害感受器中的IFN-I信号传导的伤害感受的关键调节剂。我们发现，缺乏STING或IFN-I信号传导的小鼠表现出对伤害性刺激的超敏反应和增强的伤害感受器兴奋性。相反，STING的鞘内激活在小鼠和非人灵长类动物（NHP）中产生稳健的抗伤害感受。STING介导的抗伤害感受由IFN-Is控制，其快速抑制小鼠、NHP和人类伤害感受器的兴奋性。我们的研究结果确立了STING/IFN-I信号传导轴作为生理伤害感受的关键调节器和治疗慢性疼痛的有希望的新靶点。
The innate immune regulator STING is a critical sensor of self- and pathogen-derived DNA, leading to the induction of type-I interferons (IFN-I) and other cytokines which promote immune cell-mediated eradication of pathogens and neoplastic cells . STING has also emerged as a robust driver of antitumor immunity, leading STING activators and small molecule agonists to be developed as cancer immunotherapy adjuvants . Pain, transmitted by peripheral nociceptive sensory neurons (nociceptors), also aids in host defense by alerting organisms to the presence of potentially damaging stimuli, including pathogens and cancer cells . Here, we demonstrate that STING is a critical regulator of nociception through IFN-I signaling in peripheral nociceptors. We show that mice lacking STING or IFN-I signaling exhibit hypersensitivity to nociceptive stimuli and heightened nociceptor excitability. Conversely, intrathecal activation of STING produces robust antinociception in mice and non-human primates (NHPs). STING-mediated antinociception is governed by IFN-Is, which rapidly suppress excitability of mouse, NHP, and human nociceptors. Our findings establish the STING/IFN-I signaling axis as a critical regulator of physiological nociception and a promising new target for treating chronic pain.
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DOI：
10.1073/pnas.1512832112
发表时间：
2015-12-15
影响因子：
11.1
作者：
Demaria, Olivier;De Gassart, Aude;Gilliet, Michel
通讯作者：
Gilliet, Michel
影响因子：
25
作者：
Navratilova, Edita;Porreca, Frank
通讯作者：
Porreca, Frank
DOI：
10.4049/jimmunol.1100088
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jin L;Hill KK;Filak H;Mogan J;Knowles H;Zhang B;Perraud AL;Cambier JC;Lenz LL
通讯作者：
Lenz LL
影响因子：
13.9
作者：
Costigan M;Scholz J;Woolf CJ
通讯作者：
Woolf CJ
影响因子：
5.8
作者：
Jiang C;Wang Z;Donnelly CR;Wang K;Andriessen AS;Tao X;Matsuda M;Zhao J;Ji RR
通讯作者：
Ji RR