The role of interleukin-22 in mammalian intestinal homeostasis: Friend and foe

Hedi Britt Klotskova, Evelien Kidess, Adria L. Nadal, Sylvia Brugman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


Interleukin-22 (IL-22) is an important cytokine in the intestinal environment. IL-22 is mainly produced by immune cells and targeted at nonimmune 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 antiapoptotic 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 signaling 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.

Original languageEnglish
Article numbere1144
JournalImmunity, Inflammation and Disease
Issue number2
Publication statusPublished - Feb 2024


  • cytokines
  • inflammation
  • molecular biology
  • molecules
  • mucosa
  • processes
  • techniques/approaches
  • tissues


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