Interleukin-22 Promotes Regeneration of Intestinal Epithelia

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(Last Updated On: April 4, 2020)
3D structure of interleukin-22
3D structure of interleukin-22. Image: By Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute , via Wikimedia Commons

According to a recent study, interleukin-22 can promote stem-cell-mediated regeneration of the intestinal epithelium. The present study was carried out by a team of researchers and has been published on Nature. The generation of the epithelial layers is one of the critical problems that prevent the maintenance of the organ and its function after internal injury. There are some signaling processes such as Wnt, Notch and epithelial growth factors in the intestinal stem cell that support the leucine-rich-repeat-containing G-protein-coupled receptor-5 (Lgr5+) crypt base columnar intestinal stem cells for the maintenance of normal epithelial layers.


However, the regulation of intestinal stem cell compartments during and after tissue damage is not well known. Therefore, researchers used organoid cultures for the in vivo studies where they showed significant production of the interleukin-22 by the innate lymphoid cells after the tissue injury that caused an increase in the growth of mouse and human intestinal organoids. The growth of mouse and human intestine organoids was IL-22 dependent.

Furthermore, they constructed a recombinant IL-22 directly to target intestinal stem cells and found an increase in the growth of mouse and human intestinal organoids. In addition, they also observed an increase in the proliferation and promotion of intestinal stem cell expansion. Interleukin-22 promotes the STAT3 phosphorylation in the Lgr5+ of the intestinal stem cells that is crucial for the organoid formation and regeneration.

In vivo treatment of mouse with interleukin-22 after allogeneic bone marrow transplantation caused an increase in the regeneration of epithelial cells and reduced the intestinal pathology and mortality. However, organoid cultures deficient in ATOH1, a transcription factor that activates E-box transcription, showed that interleukin-22 induces the epithelial regeneration that is independent of the Paneth cell layers.

In conclusion, this is a fundamental mechanism of the immune system that supports the intestinal epithelial cells and activates the intestinal stem cells for regeneration.

Reference: Nature journal (Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration)

Article DOI: 10.1038/nature16460

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