| First Author | Zhu P | Year | 2019 |
| Journal | Nat Immunol | Volume | 20 |
| Issue | 2 | Pages | 183-194 |
| PubMed ID | 30643264 | Mgi Jnum | J:282657 |
| Mgi Id | MGI:6381306 | Doi | 10.1038/s41590-018-0297-6 |
| Citation | Zhu P, et al. (2019) IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3. Nat Immunol 20(2):183-194 |
| abstractText | 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-13Ralpha1 (Il13ra1) in ISCs to increase its stability, which led to the expression of IL-13Ralpha1 in ISCs. IL-13 produced by group 2 innate lymphoid cells in the crypt niche engaged IL-13Ralpha1 on crypt ISCs and activated signaling mediated by IL-13IL-13R, which in turn initiated expression of the transcription factor Foxp1. Foxp1 is associated with beta-catenin in rendering its nuclear translocation, which caused activation of the beta-catenin pathway and the maintenance of Lgr5(+) ISCs. |
