IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3

P Zhu, X Zhu, J Wu, L He, T Lu, Y Wang, B Liu… - Nature …, 2019 - nature.com
P Zhu, X Zhu, J Wu, L He, T Lu, Y Wang, B Liu, B Ye, L Sun, D Fan, J Wang, L Yang, X Qin…
Nature immunology, 2019nature.com
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 …
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.
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