Open Access

Interleukin‑22 regulates the homeostasis of the intestinal epithelium during inflammation

  • Authors:
    • Xinyan Zhang
    • Shijie Liu
    • Yueqian Wang
    • Huiqiong Hu
    • Liang Li
    • Yibin Wu
    • Duo Cao
    • Yuankun Cai
    • Jiqin Zhang
    • Xueli Zhang
  • View Affiliations

  • Published online on: February 7, 2019     https://doi.org/10.3892/ijmm.2019.4092
  • Pages: 1657-1668
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interleukin‑22 (IL‑22) has both pro‑inflammatory and anti‑inflammatory 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 IL‑22 regulates tissue homeostasis through the modulation of stem cells remains unanswered. In this study, we investigated the role of IL‑22 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 IL‑22 was synchronously altered with the damage of the intestine. IL‑22 treatment promoted cell proliferation and suppressed the cell differentiation of intestinal organoids. Surprisingly, IL‑22 also led to self‑renewal defects of intestinal stem cells (ISCs), thereby eventually resulting in the death of organoids. In examining the underlying mechanisms, we found that IL‑22 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 IL‑22, which consolidated the importance of Wnt pathway at the downstream of IL‑22. Collectively, the findings of this study indicate that IL‑22 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.
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April-2019
Volume 43 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang X, Liu S, Wang Y, Hu H, Li L, Wu Y, Cao D, Cai Y, Zhang J, Zhang X, Zhang X, et al: Interleukin‑22 regulates the homeostasis of the intestinal epithelium during inflammation. Int J Mol Med 43: 1657-1668, 2019.
APA
Zhang, X., Liu, S., Wang, Y., Hu, H., Li, L., Wu, Y. ... Zhang, X. (2019). Interleukin‑22 regulates the homeostasis of the intestinal epithelium during inflammation. International Journal of Molecular Medicine, 43, 1657-1668. https://doi.org/10.3892/ijmm.2019.4092
MLA
Zhang, X., Liu, S., Wang, Y., Hu, H., Li, L., Wu, Y., Cao, D., Cai, Y., Zhang, J., Zhang, X."Interleukin‑22 regulates the homeostasis of the intestinal epithelium during inflammation". International Journal of Molecular Medicine 43.4 (2019): 1657-1668.
Chicago
Zhang, X., Liu, S., Wang, Y., Hu, H., Li, L., Wu, Y., Cao, D., Cai, Y., Zhang, J., Zhang, X."Interleukin‑22 regulates the homeostasis of the intestinal epithelium during inflammation". International Journal of Molecular Medicine 43, no. 4 (2019): 1657-1668. https://doi.org/10.3892/ijmm.2019.4092