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Interleukin-22 promotes wound repair in diabetes by improving keratinocyte pro-healing functions.

J. Invest. Dermatol. 135, 2862-2870 (2015)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Impaired re-epithelialization, imbalanced expression of cytokines and growth factors and vascular disease contribute to healing impairment in diabetes. Interleukin-22 (IL-22), a pro-inflammatory cytokine mediating crosstalk between immune system and epithelial cells, has been shown to play a role in repair processes. In this study we aimed to investigate IL-22 regenerative potential in the poor healing context of diabetic wounds. By using streptozotocin-induced diabetic mice, we demonstrated that IL-22 wound treatment significantly accelerated the healing process, by promoting re-epithelialization, and granulation tissue formation and vascularization. Improved re-epithelialization was associated with increased keratinocyte proliferation and STAT3 activation. We showed that endogenous IL-22 content was reduced at both mRNA and protein level during the inflammatory phase of diabetic wounds, with fewer IL-22-positive cells infiltrating the granulation tissue. We demonstrated that IL-22 treatment promoted proliferation and injury repair of hyperglycemic keratinocytes and induced activation of STAT3 and ERK transduction pathways in keratinocytes grown in hyperglycemic condition or isolated from diabetic patients. Finally, we demonstrated that IL-22 treatment was able to inhibit diabetic keratinocyte differentiation while promoting VEGF release. Our data indicate a pro-healing role of IL-22 in diabetic wounds, suggesting a therapeutic potential for this cytokine in diabetic ulcer management.
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Publication type Article: Journal article
Document type Scientific Article
Reviewing status