Profile of interleukin-22 in gut mucosal health and disease

Abstract

is produced by both innate and adaptive immune cells and specifically targets nonhematopoietic cells; this provides a unique mechanism linking host immunity to mucosal homeostasis and led to its establishment as a key player in the maintenance of barrier integrity at mucosal sites particularly in the gut. Our aim is to provide an overview of the role of this cytokine in maintaining gut mucosal homeostasis in the steady state and in disease. IL-22 has two main functions in healthy states: to help shape the gut microbial flora via the induction of mucins and antimicrobial peptides and to maintain barrier integrity through the induction of epithelial cell proliferation and/or survival. Given the risk of malignancy related to uncontrolled cell growth per se, it is not surprising that the expression of this cytokine is tightly regulated by a complex interactive signaling network. This consists of a combination of cytokines and various environmental signals that can be derived directly from the diet and/or the gut microbiota. A role for IL-22 in response to gut infection has been reported. Here, we will focus specifically on how reduced levels of this cytokine can exacerbate disease pathology, as in the case of human immunodeficiency virus infection. We will also review its association with inflammatory bowel disease, where its net contribution likely reflects the balance between its pro-and anti-inflammatory functions, as well as its role in malignancy, specifically colorectal cancer. Finally, we will briefly discuss the potential pros and cons of targeting IL-22 in these, and other, clinical situations.