IL‐22 in tissue‐protective therapy

Abstract

IL‐22, a member of the IL‐10 cytokine family, has recently gained significant attention as a protective agent in murine models of diseases driven by epithelial injury. Like its biochemical and functional sibling IL‐10, IL‐22 elicits cellular activation primarily by engaging the STAT3 signalling pathway. Exclusively produced by leukocytes, but targeting mostly cells of epithelial origin, IL‐22 has been proposed as a specialized cytokine messenger acting between leukocytic and non‐leukocytic cell compartments. A lack of response in leukocytes to IL‐22 mirrors tightly controlled IL‐22 receptor expression and probably explains the apparent lack of instant adverse effects after systemic IL‐22 administration to mice. Anti‐apoptotic, pro‐proliferative and pro‐regenerative characteristics the major biological properties of this cytokine. Specifically, application of IL‐22 is associated with tissue protection and/or regeneration in murine models of infection/microbe‐driven inflammation at host/environment interfaces, ventilator‐induced lung injury, pancreatitis and liver damage. Overall, preclinical studies would support therapeutic administration of seemingly well‐tolerated recombinant IL‐22 for treatment of an array of acute diseases manifested in epithelial tissues. However, the feasibility of prolonged administration of this cytokine is expected to be restricted by the tumourigenic potential of the IL‐22/STAT3 axis. IL‐22, moreover, apparently displays an inherent context‐specific capacity to amplify distinct aspects of autoimmune inflammation. Here, the prospects, expectations and restrictions of IL‐22 administration in tissue‐protective therapy are discussed.

IL-22 Ameliorates Renal Ischemia-Reperfusion Injury by Targeting Proximal Tubule Epithelium

“…5 Recombinant IL-22 is currently under development for the treatment of acute liver failure (Generon Corporation, Shanghai, China). In the current study, we provide in vivo evidence for the first time that administration of recombinant IL-22 or overexpression of IL-22 by injection of Ad-IL-22 or gene targeting ameliorates renal I/R injury and preserves renal functions by activating STAT3 and AKT in the proximal tubular epithelial cells (Figure 7).…”

“…5 Particularly, the hepatoprotective effects of IL-22 have been extensively investigated. It has been shown that administration of recombinant IL-22 significantly alleviates murine hepatic injury in response to concanavalin A, alcohol, acetaminophen, I/R, or other insults by ameliorating hepatocyte damage (reviewed in ref.…”

“…4 Accumulating evidence suggests that IL-22 possess antiapoptotic, proproliferative, and proregenerative functions. 5 Specifically, treatment with IL-22 associates with tissue protection and/or regeneration in murine models of lung injury, pancreatitis, and liver damage. 5 IL-22R1 expression was detected in the kidneys; however, what types of cells in the kidneys express this receptor and whether or not IL-22 also has a protective effect against kidney injury remain unknown.…”

“…5 Specifically, treatment with IL-22 associates with tissue protection and/or regeneration in murine models of lung injury, pancreatitis, and liver damage. 5 IL-22R1 expression was detected in the kidneys; however, what types of cells in the kidneys express this receptor and whether or not IL-22 also has a protective effect against kidney injury remain unknown. 3 AKI is a severe disorder with a rapid (ranging from hours to weeks to less than 3 months) decrease in kidney function, which occurs in 2%-7% of hospitalized patients and 5%-10% of the intensive care unit population.…”

Disease tolerance and immunity in host protection against infection

“…Pharmacologic use of cytokines that act in protective manner on parenchyma tissues, such as IL-10 114 , IL-22 115 or EGF-like factors, such as amphiregulin 15 , were also used promote disease tolerance to infections in mice.…”