STING-Dependent Signaling Underlies IL-10 Controlled Inflammatory Colitis

Abstract

<p id="P1">Intestinal immune homeostasis is preserved by commensal bacteria interacting with the host to generate a balanced array of cytokines that are essential for wound repair and for combatting infection. Inflammatory Bowel Disease (IBD), which can lead to colitis-associated cancer (CAC), is thought to involve chronic microbial irritation following a breach of the mucosal intestinal epithelium. However, the innate immune pathways responsible for regulating these inflammatory processes remain to be fully clarified. Here we show that commensal bacteria influence STING-signaling predominantly in mononuclear phagocytes to produce both pro-inflammatory cytokines as well as anti-inflammatory IL-10. Enterocolitis, manifested through loss of IL-10 was completely abrogated in the absence of STING. Intestinal inflammation was less severe in the absence of cGAS, possibly suggesting a role for cyclic dinucleotides (CDNs) indirectly regulating STING signaling. Our data sheds insight into the causes of inflammation and provides a potential therapeutic target for prevention of IBD. </p><p id="P2"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/d55560a6-031a-4064-9a9b-005939cd72e6/PubMedCentral/image/nihms929189u1.jpg"/> </div> </p>