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Interleukin-34 expression by keratinocytes is downregulated in inflamed psoriatic skin lesions: toward an immunoregulatory role in skin inflammation.
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International audience. Interleukin-34 (IL-34) expression has been widely reported in the epidermis, where the cytokine contributes to Langerhans cells homeostasis. However, little is known about its expression, regulation and role during skin inflammation. By contrast to numerous cytokines which are upregulated in inflamed skin, we show that IL-34 is downregulated in human psoriatic lesions, and restored by a successful anti-TNF biotherapy. This finding raises the hypothesis that IL-34 could exert immunoregulatory properties in the skin, as it has been already described in other physiopathological conditions. In this study, we first present the expression profiles of IL-34 and their receptors by epidermal keratinocytes and/or dermal fibroblasts cultivated in monolayer (2D) or in three-dimensions (3D). In vitro, we show that, unlike fibroblasts which do not express the cytokine, IL-34 expression is higher in 3D models of human reconstituted epidermis than in 2D monolayer cultures of keratinocytes, demonstrating that IL-34 expression is tightly associated with the level of epidermal differentiation. After stimulation by the proinflammatory cytokine oncostatin M (OSM), IL-34 expression was strongly downregulated in 2D and 3D keratinocyte cultures. This could explain our observations in psoriasis patients where an altered epidermal differentiation characterizes skin lesions. Finally, we show that IL-34 decreases OSM signaling and proinflammatory effects on the expression of target genes involved in epidermal differentiation such as cytokeratin 10 and filaggrin. Together, these results demonstrate that IL-34 is mainly expressed by differentiated keratinocytes in healthy condition but strongly downregulated during psoriasis skin inflammation and suggest its potential immunoregulatory role in the skin.
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