I am a
Home I AM A Search Login

Papers of the Week

Papers: 9 Jan 2021 - 15 Jan 2021

Animal Studies

2021 Jan 13


Editor's Pick

STING controls nociception via type I interferon signalling in sensory neurons.


Donnelly CR, Jiang C, Andriessen AS, Wang K, Wang Z, Ding H, Zhao J, Luo X, Lee MS, Lei YL, Maixner W, Ko M-C, Ji R-R
Nature. 2021 Jan 13.
PMID: 33442058.


The innate immune regulator STING is a critical sensor of self- and pathogen-derived DNA. DNA sensing by STING leads to the induction of type-I interferons (IFN-I) and other cytokines, which promote immune-cell-mediated eradication of pathogens and neoplastic cells. STING is also a robust driver of antitumour immunity, which has led to the development of STING activators and small-molecule agonists as adjuvants for cancer immunotherapy. Pain, transmitted by peripheral nociceptive sensory neurons (nociceptors), also aids in host defence 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 signalling in peripheral nociceptors. We show that mice lacking STING or IFN-I signalling exhibit hypersensitivity to nociceptive stimuli and heightened nociceptor excitability. Conversely, intrathecal activation of STING produces robust antinociception in mice and non-human primates. STING-mediated antinociception is governed by IFN-Is, which rapidly suppress excitability of mouse, monkey and human nociceptors. Our findings establish the STING-IFN-I signalling axis as a critical regulator of physiological nociception and a promising new target for treating chronic pain.