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.
Highlights
IL-22 is a member of the IL-10 cytokine family, and is mainly produced by activated CD4+ T cells and NK cells [1, 2]
ultraviolet B (UVB) irradiation increases the expression of IL-22Rα in human keratinocytes
IL-22Rα mRNA expression increased in a time-dependent manner following UVB irradiation, whereas IL-10Rβ, a co-receptor of IL-22Rα to form functional IL-22R, was constitutively expressed (Fig 1B–1E)
Summary
IL-22 is a member of the IL-10 cytokine family, and is mainly produced by activated CD4+ T cells and NK cells [1, 2]. Its receptor (IL-22R) consists of two subunits, IL-22Rα and IL-10Rβ. The IL-10Rβ subunit is expressed ubiquitously, but the expression of the IL-22Rα subunit is mainly restricted to non-hematopoietic tissues such as the skin, pancreas, intestine, liver, lung, eye, and kidney [3, 4]. There are recent reports that it is expressed on activated. Interleukin-22 and UVB-induced skin inflammation macrophages [5]. Since the biological activity of IL-22 is initiated by binding to IL-22Rα, it is important to track the expression of IL-22Rα in order to understand the actions of IL-22
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