All in all, IL-22 has been shown to have both positive and negative
effects in the mammalian intestine, suggestive of a complex regulation
of this cytokine to ensure homeostasis in the gut (summarized in Figure
1). The conditions defining the outcome of IL-22 signalling in the
intestine include the location in the intestine, the concentration of
IL-22, timing and duration, the cellular source of IL-22, and the
presence of IL-22 regulators. Additionally, it matters whether IL-22 is
present on the apical or basolateral side of epithelial cells. To
conclude, IL-22 is an appealing therapeutic agent as well as a target to
help restore intestinal homeostasis, but careful consideration should be
given when adopting IL-22 or IL-22 signalling targeted
strategies
as there are many conditions which define its effect in the mammalian
gut.
Figure 1 : Beneficial and harmful effects of IL22 in the
intestine. IL-22 is produced by various immune cells at the intestinal
epithelium. Here, it acts on enterocytes by binding to the IL-22
receptor complex to initiate its effects. These include inducing cell
proliferation/tumorigenesis, wound healing, and induction of mucins by
Goblet cells and antimicrobial peptides by Paneth cells. If produced in
excessive amounts, these antimicrobial peptides may damage the
intestinal epithelium and reduce microbial diversity. IL-22 induces
tight junction proteins, modulating epithelial barrier permeability.
IL-22 also induces Paneth cells differentiation in humans. IL-22 is
tightly regulated by several factors (Box 1)(figure created with
BioRender).