The role of interleukin-22 in mammalian intestinal homeostasis; friend
and foe.
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.