IL-22: There Is a Gap in Our Knowledge

Abstract

IL-22 is a critical cytokine in modulating tissue responses during inflammation. IL-22 is upregulated in many chronic inflammatory diseases, making IL-22 biology a potentially rewarding therapeutic target. However, this is complicated by the dual-natured role of IL-22 in inflammation, as the cytokine can be protective or inflammatory depending on the disease model. Although scientific interest in IL-22 has increased considerably in the past 10 y, there is still much we do not know about the environmental, cellular, and molecular factors that regulate the production and function of this cytokine. A better understanding of IL-22 biology will allow us to develop new or improved therapeutics for treating chronic inflammatory diseases. In this article, I will highlight some of the outstanding questions in IL-22 biology.

Regulation of IL-22 biology is directed by many routes

IL-22 is mainly produced by CD4 T cells and ILC3s (top left) and regulated by the transcription factors STAT3, AHR and MAPKs. Many environmental factors control this production, including commensal bacteria (top right). Secreted IL-22 stimulates GI tract epithelial cells (bottom left) leading to STAT3 activation and production of mucins, antimicrobial proteins, as well as increasing cellular proliferation and fucosylation. These factors in turn regulate the commensal bacteria. DCs (bottom right) are a source of IL-22 binding protein (IL-22BP), an IL-22 receptor homolog, which binds to IL-22 with higher affinity than the IL-22 receptor and inhibits IL-22-mediated signaling in target cells. Although many regulatory factors are known for each of these routes, many gaps in our knowledge exist, as represented by question marks (?). Figure generated using Servier Medical Art.