Interleukin 34 exerts anti-inflammatory activities on keratinocytes and is down-regulated in psoriatic-inflamed skin
Résumé
Although interleukin-34 (IL-34) expression has been originally reported in the skin to play a role in Langerhans cell (LC) homeostasis, less is known about its contribution to skin inflammation. Here, we have investigated the cutaneous expression, regulation and role of IL-34 in psoriasis, as well as the expression of its receptors CSF-1R, PTPRZ1 and Syndecan-1. We showed that IL-34 expression is markedly decreased in psoriatic skin compared to healthy skin and restored after a successful anti-TNFα treatment. Consistent with its role in the maintenance of LC within the epidermis, the lowered expression of IL-34 was associated with a reduced density of LC. We identified a correlation between IL-34 and cytokeratin 10 or filaggrin expressions, suggesting a link with epidermal differentiation. In vitro experiments using primary keratinocytes cultured in monolayer or differentiated into reconstituted human epidermis confirmed that IL-34 expression is associated to the level of epidermal differentiation. When exposed to proinflammatory cytokines, keratinocytes underwent IL-34 downregulation. Finally, we demonstrated that IL-34 counteracts the proinflammatory effects of oncostatin M on epidermal differentiation by modulating STAT3 signaling pathway. In conclusion, IL-34 has regulatory properties in the skin by directly targeting keratinocytes and is downregulated by proinflammatory cytokines in inflamed skin during psoriasis.
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