GSDMD and inflammatory bowel disease: In addition to its activation in intestinal epithelial cells, GSDMD is also activated in colonic macrophages independent of the gut microbiota, making it protective in DSS-induced colitis.31 GSDMD−/− mice treated with DSS exhibit more colitis phenotype, including shorter colon length and more body weight loss on day 9 compared to WT mice by exacerbating cGAS inflammation.31 The use of cGAS inhibitor RU.521 in the DSS-treated mice attenuates colitis phenotypes in WT mice but completely abolishes them in GSDMD−/− mice, making it a potential target for protection from IBD.31