Oncostatin M (OSM) has been reported to be overexpressed in psoriasis skin lesions and to exert proinflammatory effects in vitro on human keratinocytes. Here, we report the proinflammatory role of OSM in vivo in a mouse model of skin inflammation induced by intradermal injection of murine OSM-encoding adenovirus (AdOSM) and compare with that induced by IL-6 injection. Here, we show that OSM potently regulates the expression of genes involved in skin inflammation and epidermal differentiation in murine primary keratinocytes. In vivo, intradermal injection of AdOSM in mouse ears provoked robust skin inflammation with epidermal thickening and keratinocyte proliferation, while minimal effect was observed after AdIL-6 injection. OSM overexpression in the skin increased the expression of the S100A8/9 antimicrobial peptides, CXCL3, CCL2, CCL5, CCL20, and Th1/Th2 cytokines, in correlation with neutrophil and macrophage infiltration. In contrast, OSM downregulated the expression of epidermal differentiation genes, such as cytokeratin-10 or filaggrin. Collectively, these results support the proinflammatory role of OSM when it is overexpressed in the skin. However, OSM expression was not required in the murine model of psoriasis induced by topical application of imiquimod, as demonstrated by the inflammatory phenotype of OSM-deficient mice or wild-type mice treated with anti-OSM antibodies.Keywords: Imiquimod · Keratinocyte · Oncostatin M · Psoriasis · Skin inflammation Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Jean-François Jégou e-mail: jean-francois.jegou@univ-poitiers.fr IntroductionPsoriasis is the most common inflammatory skin disease affecting 2-3% of the adult population, mainly in developed countries, Eur. J. Immunol. 2016Immunol. . 46: 1737Immunol. -1751 in which patients develop skin lesions characterized by erythematous and scaly plaques [1]. The histological features of psoriatic skins are a thickening of the epidermis resulting from an altered keratinocyte differentiation associated with a hyperplasia at the basement membrane, a hyperkeratosis and a parakeratosis (loss of the granular layer and abnormal presence of cell nuclei in the cornified layer) [1,2]. At the inflammatory site, these alterations of the epidermis are the consequence of a crosstalk between infiltrating immune cells and tissue resident cells (e.g. dermal fibroblasts, epidermal keratinocytes, and resident immune cells) through the release of numerous cytokines. In this complex network of interactions, keratinocytes are now considered to play a key role as bona fide innate immune cells, capable of secreting cytokines, chemokines, and antimicrobial peptides in response to various stimuli [3]. Psoriasis has been reported to be a Th1-and Th17-driven pathology [4]. The IL-23/IL-17 axis plays a crucial role in the pathogenesis of the disease, as demonstrated by the detection of IL-23 producing DCs and the expression of IL-17 and IL-22 by T cells and type 3...

No abstract