The pathogenic role of interleukin-22 and its receptor during UVB-induced skin inflammation

Abstract

Recent studies show that IL-22, a cytokine produced by activated CD4+ T cells and NK cells, plays a pathogenic role in acute and chronic skin diseases. While IL-22 is produced by immune cells, the expression of IL-22Rα, the functional subunit of IL-22R, is mostly restricted to non-hematopoietic cells in organs such as the skin and pancreas. Although it is well known that ultraviolet B (UVB) radiation induces skin inflammation, there have been no reports regarding the effect of UVB on the expression of IL-22Rα. This study investigated IL-22Rα expression and IL-22-mediated proliferation and pro-inflammatory cytokine production by UVB-irradiated keratinocytes. IL-22Rα was increased in HaCaT and primary human keratinocytes after UVB irradiation through the translocation of IL-22Rα from the cytosol to the membrane. This increase in the expression of IL-22Rα was mediated by the PI3K/Akt pathway. Moreover, the suppression of keratinocyte proliferation by UVB irradiation was inhibited by treatment with IL-22. At the same time, IL-22 increased the production of IL-1α, IL-6, and IL-18 in UVB-irradiated HaCaT cells and primary human keratinocytes. Finally, IL-22Rα expression was increased in UVB-irradiated human and mouse skin by immunohistochemistry. The increased expression of IL-22Rα therefore promotes keratinocyte proliferation and pro-inflammatory cytokine production during UVB-induced skin inflammation, suggesting that UVB facilitates skin inflammation by increasing the responsiveness of keratinocytes to IL-22. This study provides a new insight into UVB-induced skin inflammation and the regulation of related inflammatory skin diseases.

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

“…CSA (Cyclosporin) is involved in increasing the Squamous Cell Carcinoma (SCC) by favoring polarization of Th22 which results in increased IL-22 production and thus the blockage of IL22 by using anti-IL-22 antibody could potentially become a viable therapeutic option (31). Keratinocyte's response to IL22 is increased by UVB resulting in skin inflammation (171). Another in vitro study reveals that IL-22 and IL22R1 expression is enhanced in tumorous and peri-tumorous tissues, where cellular proliferation may be encouraged by IL-22 (172).…”

Interleukin-22 and keratinocytes; pathogenic implications in skin inflammation

“…House dust mites increase IL-22R1 expression and enhance the effects of IL-22 in keratinocytes [91]. UVB irradiation enhances the translocation of IL-22R1 from the cytosol to the membrane, and upregulates the responsiveness of keratinocytes to IL-22 [92]. IL-22 stimulates keratinocytes to produce IL-19, IL-20 and IL-24 [69].…”

Radiation-induced skin injury: pathogenesis, treatment, and management

“…Proinflammatory cytokines are critical to the adverse effects of early and late ionizing radiation. Inflammatory bodies are capable of maturing the pro-inflammatory cytokines (IL-6, IL-18, IL-22, and IL-1β), as well as exacerbating radiation damage [ 70 – 72 ]. It can be seen that inhibiting the expression of inflammatory factors can promote skin repair.…”