The RNA helicase Dhx15 mediates Wnt-induced antimicrobial protein expression in Paneth cells
Yalong Wang, Kaixin He, Baifa Sheng, Xuqiu Lei, Wanyin Tao, Xiaoliang Zhu, Zheng Wei, Rongjie Fu, Anlei Wang, Shengdan Bai, Zhao Zhang, Na Hong, Chao Ye, Ye Tian, Jun Wang, Mingsong Li, Kaiguang Zhang, Lin Li, Hua Yang, Huabing Li, Richard A. Flavell, Shu Zhu
Abstract
Significance RNA helicases play critical roles in multiple biological processes. However, little in vivo data are available because of the lethality of mice completely deficient in RNA helicases. Here, we generate mice with conditional knockout of DEAD-box Helicase 15 (Dhx15) in the intestine, in which we found a specific defect in antimicrobial peptide (AMP) α-defensins in Paneth cells. Additionally, we found that Dhx15-specific depletion in the intestine leads to susceptibility to enteric bacterial infection as well as dextran sulfate sodium-induced colitis in mice. In humans, we also found reduced protein levels of Dhx15 in ulcerative colitis patients.