A Double Edged Sword Role of Interleukin-22 in Wound Healing and Tissue Regeneration

Abstract

Wound healing and tissue regeneration is an intricate biological process that involves repair of cellular damage and maintenance of tissue integrity. Cascades involved in wound healing and tissue regeneration highly overlap with cancer causing pathways. Usually, subsequent tissue damage events include release of a number of cytokines to accomplish post-trauma restoration. IL-22 is one of the cytokines that are immediately produced to initiate immune response against several tissue impairments. IL-22 is a fundamental mediator in inflammation, mucous production, protective role against pathogens, wound healing, and tissue regeneration. However, accumulating evidence suggests pivotal role of IL-22 in instigation of various cancers due to its pro-inflammatory and tissue repairing activity. In this review, we summarize how healing effects of IL-22, when executed in an uncontrollable fashion can lead to carcinogenesis.

Amelioration of DSS-induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

“…[5,7,14,15] In this regard, IL-22 regulates intestinal epithelial regeneration and intestinal barrier function by regulating junction protein expression and secretion of antimicrobial peptide and proteins including S100 and RegIII. [7,16,26] Previous studies have shown that IL-22 increases in inflammatory bowel disease (IBD) patients, but the disease was not dramatically improved. This may be due to the insufficient function of IL-22 by the inhibition of IL-22 binding protein (IL-22BP), a natural antagonist of IL-22, suggesting that extremely large amount of IL-22 may be required to overcome the IL-22BP-mediated inhibition.…”

“…IL-22 is a major regulatory cytokine for maintaining the homeostasis of epithelial cells in the intestine. [5,7,14,15] In this regard, IL-22 regulates intestinal epithelial regeneration and intestinal barrier function by regulating junction protein expression and secretion of antimicrobial peptide and proteins including S100 and RegIII. [7,16,26] Previous studies have shown that IL-22 increases in inflammatory bowel disease (IBD) patients, but the disease was not dramatically improved.…”

“…This may be due to the insufficient function of IL-22 by the inhibition of IL-22 binding protein (IL-22BP), a natural antagonist of IL-22, suggesting that extremely large amount of IL-22 may be required to overcome the IL-22BP-mediated inhibition. [7,30,38,44] Indeed, several reports suggested that administration of IL-22 or IL-22Fc fusion protein exhibited sufficient protection against DSS-induced colitis in preclinical models. [15,45,46] On the contrary, however, blockade of IL-22 by neutralization antibody improved colitis induced by agonist anti-CD40 Ab or DNBS, suggesting complex role of IL-22 in intestinal inflammation and barrier function.…”

“…[26,40] The levels of pro-inflammatory cytokines and chemokines including IL-1β, IL-6, IL-17A, C-X-C motif chemokine ligand 1 (CXCL1) and C-C motif chemokine ligand 2 (CCL2) were also highly elevated by DSS administration. [7] The intraperitoneal injection of IL-22 prevented body weight loss and reduced colon length shortening. In addition, the level of IL-6, IL-17A and CCL2 significantly reduced by IL-22 treatment (Figure 4d).…”

“…[12,13] IL-22R1 has high-binding affinity toward IL-22 and is restrictedly expressed on epithelial cells unlike IL-10R2 expressed ubiquitously. [7] Therefore, the major target organs of IL-22 are generally considered as liver, pancreas, lung, colon, intestine and kidney in which epithelial cells cooperatively form a continuous physical barrier to allow tightly regulated cellular transport and prevent pathogen infections. [3] As pleiotropic functions of IL-22 have been elucidated, many studies have demonstrated the therapeutic potential of IL-22 in liver and pancreas regeneration, infection prevention and graft-versus-host disease.…”