Systemic sclerosis (SSc) is a connective tissue disease characterized by autoimmunity, vasculopathy, and fibrosis. Several studies demonstrated the involvement of various cytokines including IL-1 in SSc. IL-36 cytokines, a subgroup of IL-1 family, comprise IL-36α, β, γ, IL-36Ra, and IL-38. IL-36α, β, γ are known to promote inflammatory response, which is mainly produced by epithelial cells. Whereas, IL-36Ra as well as IL-38 may have anti-inflammatory effect. Recent reports suggest that epidermis may play an important role in the pathogenesis of SSc, although the involvement of IL-36 family is still unclear. Thus, we focused on IL-36 family regarding its level and function in SSc. IL-36α, β, γ and IL-38 expressions were evaluated by immunohistochemistry in skin tissue from SSc patients and healthy controls, and for IL-36γ by western blot analysis. Serum IL-36γ levels were evaluated by ELISA in 61 patients with SSc and controls. As results, IL-36γ expression levels were significantly higher in epidermis of SSc patients compared to that in controls and sera of SSc patients also had increased levels of IL-36γ. To analyze a role of IL-36γ in SSc, cultured healthy keratinocytes were stimulated with IL-36γ, and expression levels of epithelial-mesenchymal transition (EMT)-related factors were analyzed by qRT-PCR and Immunofluorescence. Expression levels of E-cadherin were significantly downregulated while that of Slug and Vimentin were increased in IL-36γ-stimulated keratinocytes with or without TGFβ than that in controls. Furthermore, skin fibroblasts in the presence of IL-36γ significantly induced Egr-1 expression. In conclusion, increased levels of IL-36γ in epidermis may be involved in the fibrotic pathogenesis of SSc by inducing EMT.

ESDR041 - Increased Interleukin-36γ in keratinocytes may induce epithelial-mesenchymal transition in patients with systemic sclerosis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.