STING controls nociception via type I interferon signalling in sensory neurons

Christopher R. Donnelly (), Changyu Jiang, Amanda S. Andriessen, Kaiyuan Wang, Zilong Wang, Huiping Ding, Junli Zhao, Xin Luo, Michael S. Lee, Yu L. Lei, William Maixner, Mei-Chuan Ko and Ru-Rong Ji ()
Additional contact information
Christopher R. Donnelly: Duke University Medical Center
Changyu Jiang: Duke University Medical Center
Amanda S. Andriessen: Duke University Medical Center
Kaiyuan Wang: Duke University Medical Center
Zilong Wang: Duke University Medical Center
Huiping Ding: Wake Forest School of Medicine
Junli Zhao: Duke University Medical Center
Xin Luo: Duke University Medical Center
Michael S. Lee: Duke University Medical Center
Yu L. Lei: University of Michigan
William Maixner: Duke University Medical Center
Mei-Chuan Ko: Wake Forest School of Medicine
Ru-Rong Ji: Duke University Medical Center

Nature, 2021, vol. 591, issue 7849, 275-280

Abstract: Abstract 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 cells1,2. 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 immunotherapy3. 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 cells4,5. 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-020-03151-1 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:591:y:2021:i:7849:d:10.1038_s41586-020-03151-1

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-03151-1

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().