IEC Dhx15 KO RNA sequencing

RNA helicases play roles in various essential biological processes such as RNA splicing and editing. Recent in vitro studies show that RNA helicases are involved in immune responses toward viruses, serving as viral RNA sensors or immune signaling adaptors. However, there is still a lack of in vivo data to support the tissue- or cell-specific function of RNA helicases owing to the lethality of mice with complete knockout of RNA helicases; further, there is a lack of evidence about the anti-bacterial role of helicases. Here, we investigated the in vivo role of Dhx15 in intestinal anti-bacterial responses by generating mice that were intestinal epithelial cell (IEC)- specific-deficient for Dhx15 (Dhx15 f/f Villin1-cre, Dhx15deltaIEC). These mice are susceptible to infection with enteric bacteria Citrobacter rodentium (C. rod), owing to impaired alpha-defensin production by Paneth cells. Moreover, mice with Paneth cell-specific depletion of Dhx15 (Dhx15 f/f Defensin alpha 6-cre, Dhx15deltaPaneth) are more susceptible to DSS(Dextran Sodium Sulfate)-induced colitis, which phenocopy Dhx15deltaIEC mice, due to the dysbiosis of the intestinal microbiota. In humans, reduced protein levels of Dhx15 are found in UC patients. Taken together, our findings identify a key regulator of Wnt-induced alpha-defensins in Paneth cells, and offer novel insights into its role in the anti-microbial response as well as intestinal inflammation.