IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3
Pingping Zhu, Xiaoxiao Zhu, Jiayi Wu, Luyun He, Tiankun Lu, Yanying Wang, Benyu Liu, Buqing Ye, Lei Sun, Dongdong Fan, Jing Wang, Liuliu Yang, Xiwen Qin, Ying Du, Chong Li, Lei He, Weizheng Ren, Xin Wu, Yong Tian & Zusen Fan
Abstract
Intestinal stem cells (ISCs) are maintained by stemness signaling for precise modulation of self-renewal and differentiation under homeostasis. However, the way in which intestinal immune cells regulate the self-renewal of ISCs remains elusive. Here we found that mouse and human Lgr5+ ISCs showed high expression of the immune cell–associated circular RNA circPan3 (originating from the Pan3 gene transcript). Deletion of circPan3 in Lgr5+ ISCs impaired their self-renewal capacity and the regeneration of gut epithelium in a manner dependent on immune cells. circPan3 bound mRNA encoding the cytokine IL-13 receptor subunit IL-13Rα1 (Il13ra1) in ISCs to increase its stability, which led to the expression of IL-13Rα1 in ISCs. IL-13 produced by group 2 innate lymphoid cells in the crypt niche engaged IL-13Rα1 on crypt ISCs and activated signaling mediated by IL-13？IL-13R, which in turn initiated expression of the transcription factor Foxp1. Foxp1 is associated with β-catenin in rendering its nuclear translocation, which caused activation of the β-catenin pathway and the maintenance of Lgr5+ ISCs.
附件下载：
IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3, Nature Immu, 14 Jan 2019
Nature Immunology, 14 January, 2019， DOI: http://dx.doi.org/10.1038/s41590-018-0297-6
IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3
Pingping Zhu, Xiaoxiao Zhu, Jiayi Wu, Luyun He, Tiankun Lu, Yanying Wang, Benyu Liu, Buqing Ye, Lei Sun, Dongdong Fan, Jing Wang, Liuliu Yang, Xiwen Qin, Ying Du, Chong Li, Lei He, Weizheng Ren, Xin Wu, Yong Tian & Zusen Fan
Abstract
Intestinal stem cells (ISCs) are maintained by stemness signaling for precise modulation of self-renewal and differentiation under homeostasis. However, the way in which intestinal immune cells regulate the self-renewal of ISCs remains elusive. Here we found that mouse and human Lgr5+ ISCs showed high expression of the immune cell–associated circular RNA circPan3 (originating from the Pan3 gene transcript). Deletion of circPan3 in Lgr5+ ISCs impaired their self-renewal capacity and the regeneration of gut epithelium in a manner dependent on immune cells. circPan3 bound mRNA encoding the cytokine IL-13 receptor subunit IL-13Rα1 (Il13ra1) in ISCs to increase its stability, which led to the expression of IL-13Rα1 in ISCs. IL-13 produced by group 2 innate lymphoid cells in the crypt niche engaged IL-13Rα1 on crypt ISCs and activated signaling mediated by IL-13？IL-13R, which in turn initiated expression of the transcription factor Foxp1. Foxp1 is associated with β-catenin in rendering its nuclear translocation, which caused activation of the β-catenin pathway and the maintenance of Lgr5+ ISCs.
文章链接：https://www.nature.com/articles/s41590-018-0297-6