Gasdermin C links nutrient and immune signaling to protist-induced type 2 immunity and intestinal repair
Year: 2025
Type: preprint
Abstract: SUMMARY The Gasdermin family of proteins has recently been implicated in tissue repair and homeostasis through their effector function in type 2 immunity and pyroptosis. Yet the role of Gasdermin C proteins has not been fully characterized in the mammalian intestine, where environmental factors can influence epithelial regeneration and repair. Here we report that Gsdmc2-4 genes are regulated in a nutrient-dependent manner and are suppressed with aging. We uncover that commensal protists in the gut regulate Gsdmc2-4 expression through activation of type 2 immune responses. In intestinal organoid experiments, we find that STAT6 is necessary for Gsdmc2-4 induction in response to type 2 cytokines; however, basal expression of Gsdmc2-4 in vivo is only partially diminished in Stat6 knockout animals. Finally, in protist-colonized animals, loss of Gsdmc1-4 exacerbated mucosal erosion and inflammation in response to Dextran sodium sulfate (DSS) exposure, implicating these proteins in coordinating epithelial responses to injury.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1858189645, Understanding the Mechanisms of Age-Dependent Decline of Intestinal Stem Cell Function, G36614667, Multidisciplinary Training in Ethnic Diversity and Cancer Disparities, Cellular, molecular, and biochemical sciences training grant, G9000266250, Training Program for Cancer Prevention and Control, Cancer Center Support Grant, Identification of novel type III IFN regulatory pathways
OpenAlex ID: W4414575610