STING promotes intestinal antimicrobial peptide REG3γ expression in epithelial cells via STAT3 activation and glycolysis, protecting against enteric infection and colitis.
REG3γspecific antimicrobial peptide upregulated by STING signaling to protect intestinal homeostasis
What the researchers found
STING-/- mice showed increased susceptibility to C. rodentium infection with impaired bacterial clearance and lower REG3γ expression. STING agonists activated STAT3 and glycolysis in intestinal epithelial cells to promote REG3γ production, and 2,3-cGAMP treatment inhibited colitis in vivo.
Why it matters
Understanding how the gut maintains its antimicrobial defenses could lead to new treatments for inflammatory bowel disease and gut infections. STING agonists, already being developed for cancer immunotherapy, could be repurposed for gut health applications.
The numbers in context
STING-/- mice: more severe inflammation, impaired bacterial clearance, reduced antimicrobial peptide expression vs WT.
How the study worked
STING knockout mice infected with Citrobacter rodentium. STING agonists (CMA, DMXAA, 2,3-cGAMP) tested on intestinal epithelial cells. REG3γ-deficient cells used for pathway confirmation. STAT3 and glycolysis inhibitors used to confirm mechanism.
Who was studied
STING-knockout and wild-type mice infected with Citrobacter rodentium
What this study cannot tell us
Mouse model with C. rodentium — relevance to human enteric pathogens needs validation. STING agonist effects may differ in human intestinal epithelium. Long-term effects of STING activation on gut homeostasis unknown.
How to read the evidence
Well-designed animal study with knockout mice, multiple STING agonists, and pathway-specific inhibitor controls. Mechanistic clarity is strong but human validation is needed.
When this study was published
Published in 2020. STING biology in mucosal immunity continues to be an expanding research area.
The bigger picture
The connection between innate immune sensing (STING) and antimicrobial peptide production reveals a sophisticated defense system in the gut. As STING agonists are developed for cancer treatment, this gut-protective role could be an important additional benefit or guide dosing considerations.
Questions still open
- Could STING agonists be used therapeutically for inflammatory bowel disease?
- Does STING-mediated REG3γ production play a role in human gut health?
- Would STING activation have unintended pro-inflammatory effects with chronic use in the gut?
Common questions
What is STING?
What is REG3γ?
Read the original research
STING controls intestinal homeostasis through promoting antimicrobial peptide expression in epithelial cells.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(11), 15417-15430
Citation
Yu, Yanbo; Yang, Wenjing; Bilotta, Anthony J; Yu, Yu; Zhao, Xiaojing; Zhou, Zheng; Yao, Suxia; Xu, Jimin; Zhou, Jia; Dann, Sara M; Li, Yanqing; Cong, Yingzi. (2020). STING controls intestinal homeostasis through promoting antimicrobial peptide expression in epithelial cells.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(11), 15417-15430. https://doi.org/10.1096/fj.202001524R