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The role of interleukin-22 in mammalian intestinal homeostasis; friend and foe.
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  • Hedi-Britt Klotskova,
  • Evelien Kidess,
  • Adria Lopez Nadal,
  • Sylvia Brugman
Hedi-Britt Klotskova
Wageningen Universiteit en Research
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Evelien Kidess
Wageningen Universiteit en Research
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Adria Lopez Nadal
Wageningen Universiteit en Research
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Sylvia Brugman
Wageningen Universiteit en Research

Corresponding Author:[email protected]

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Abstract

Interleukin-22 (IL-22) is an important cytokine in the intestinal environment. IL-22 is mainly produced by immune cells and targeted at non-immune cells such as epithelial and stromal cells in a broad array of tissues such as -but not restricted to- the liver and adipose tissue. IL-22 therefore connects immune functions with metabolic functions of the host, and since it is induced by the microbiota, connects host functioning to the outside environment. IL-22 induces epithelial cell proliferation aiding in rapid epithelium regeneration and wound healing. Additionally, IL-22 activates anti-apoptotic genes and DNA damage response pathways, enhancing epithelial cell survival. Recently, it has also been shown that IL-22 induces Paneth cell differentiation in humans. However, IL-22 can also contribute to intestinal epithelium damage and reduces microbial diversity in the intestine directly or indirectly by inducing excessive antimicrobial peptide production by epithelial cells. Moreover, IL-22 enhances angiogenesis and may therefore support tumorigenesis in the intestine. In conclusion, it appears that whether IL-22 has a beneficial or harmful effect in the mammalian intestine largely depends on its regulation. This review aims to provide a comprehensive overview of the current literature and emphasizes that IL-22 signalling outcome depends on the timing and duration of IL-22 production, the presence of it regulators such as IL-22BP, and the specific location of the cytokine production in the gastrointestinal tract.
22 Sep 2023Submitted to Immunity, Inflammation and Disease
27 Sep 2023Submission Checks Completed
27 Sep 2023Assigned to Editor
27 Sep 2023Review(s) Completed, Editorial Evaluation Pending
05 Oct 2023Reviewer(s) Assigned
09 Nov 2023Editorial Decision: Revise Minor