Role of stimulator of interferon genes (STING) in the enteric nervous system in health and disease

Abstract Stimulator of Interferon Genes (STING) is a crucial protein that controls the immune system's reaction to bacterial and viral infections. As a pattern‐recognition receptor, STING is found in immune cells as well as in neurons and glia in the enteric nervous system (ENS). Recent studies have linked STING to the pathogenesis of several neurological disorders like multiple sclerosis (MS), Alzheimer's disease (AD), and gastrointestinal disorders, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), which are characterized by chronic inflammation and dysregulation of the enteric nervous system (ENS) in the digestive tract. STING plays a crucial role in the pathway that induces the production of interferon in response to viral infection in the central nervous system (CNS). A new study by Dharshika et al. in the current issue of Neurogastroenterology and Motility has demonstrated distinct roles for STING in enteric neurons and glia, namely activation of STING leads to IFN‐β production in enteric neurons but not in glia and reducing STING activation in enteric glia does not modulate the severity of Dextran sulfate sodium (DSS) colitis or subsequent loss of enteric neurons. Rather, the role of STING in enteric glia is related to enhancing autophagy. STING can influence gastrointestinal motility and barrier function and therefore be involved in the pathophysiology of IBS and IBD. This mini review highlights the current knowledge of STING in the pathophysiology of CNS and gastrointestinal diseases as well as these newly uncovered roles STING in enteric neurons and glia.