Role of STING in gut homeostasis and inflammation

STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING-/- mice presented defective protective mechanisms of intestinal mucosa including decreased number of goblet cells, diminished mucus production and lower levels of SIgA when compared to wild-type (WT) mice. Fecal content was able to activate STING, indicating a role of this molecule in gut. We also observed that absence of STING lead to increase in ILC1 as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING-/- mice. Moreover, these mice were highly susceptible to DSS-induced colitis, showing increased mortality and morbidity when compared to WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in experimental colitis.