| First Author | Zhang X | Year | 2019 |
| Journal | Int J Mol Med | Volume | 43 |
| Issue | 4 | Pages | 1657-1668 |
| PubMed ID | 30816423 | Mgi Jnum | J:378247 |
| Mgi Id | MGI:6459340 | Doi | 10.3892/ijmm.2019.4092 |
| Citation | Zhang X, et al. (2019) Interleukin22 regulates the homeostasis of the intestinal epithelium during inflammation. Int J Mol Med 43(4):1657-1668 |
| abstractText | Interleukin22 (IL22) has both proinflammatory and antiinflammatory properties in a number tissues depending on the environment. Epithelial cells usually have a rapid turnover and are fueled by tissue stem cells. However, the question of whether IL22 regulates tissue homeostasis through the modulation of stem cells remains unanswered. In this study, we investigated the role of IL22 in the homeostasis of intestinal epithelial cells (IECs) during inflammation through a 3D organoid culture system. qPCR was performed to detect the changes in important gene transcriptions, and immunohistochemistry and western blot analysis were carried out to determine protein expression. As a result, we found that the expression of IL22 was synchronously altered with the damage of the intestine. IL22 treatment promoted cell proliferation and suppressed the cell differentiation of intestinal organoids. Surprisingly, IL22 also led to selfrenewal defects of intestinal stem cells (ISCs), thereby eventually resulting in the death of organoids. In examining the underlying mechanisms, we found that IL22 activated signal transducer and activator of transcription 3 (Stat3) phosphorylation and suppressed the Wnt and Notch signaling pathways. Importantly, Wnt3a treatment attenuated the organoid defects caused by IL22, which consolidated the importance of Wnt pathway at the downstream of IL22. Collectively, the findings of this study indicate that IL22 regulates the homeostasis of the intestinal epithelium and is critical for the regeneration of the intestine during inflammation. Thus, the data of this study may provide a potential strategy and a basis for the treatment of diseases of intestinal inflammation in clinical practice. |
