414 Identification of sebocytes as a novel source for adipokines within human skin

Abstract

412 Characterization of the immunomodulatory effects of sebocytes on macrophages M Lovaszi, M Mattii, K Eyerich, D Kovacs, C Zouboulis, M Stahle, S Eyerich and D Torocsik 1 Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, 2 ZAUM e Center for Allergy and Environment, Technische Universitat and Helmholtz Center Munich, Munich, Germany, 3 Department of Dermatology and Allergy, Technische Universitat Munich, Munich, Germany, 4 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany and 5 Unit of Dermatology and Venereology, Department of Medicine, Karolinska lnstitutet, Karolinska University Hospital, Stockholm, Sweden Macrophages surround the sebaceous glands both in the healthy and the inflamed pilosebaceous unit; however, the reason for this phenomenon and the possible role of sebocytes in it has not yet been investigated. By performing immunohistochemistry on healthy biopsies, we could demonstrate that macrophages in the close proximity of sebaceous glands are exclusively alternatively activated (CD163/FXIII-A/CD206/CD209). To investigate if sebocytes contribute to the differentiation, polarization and function of macrophages, human peripheral blood monocytes were differentiated and activated in the presence of either supernatant from the human SZ95 sebocyte cell line, or major sebum lipid components such as oleic-, linoleic-, palmitic-, stearicacids and squalene. Our results showed that with the secretion of CXCL8, sebocytes could exert a chemoattractant effect towards monocytes, while sebocytes derived lipids promoted monocyte differentiation into alternatively activated macrophages as marked by the up-regulation of CD206, CD209 and FXIII-A. Moreover, detection of the produced IL-1b, IL-6 and TNFa protein levels by Propionibacterium acnes activated macrophages revealed a selective inflammatory effect for the various sebum lipids. Our results altogether suggest a role for sebaceous glands in initiating and modulating innate immune responses via their proteins and lipids that are of possible pathologic and therapeutic relevance. 413 Epithelial resident and infiltrating dendritic cells amplify active and resolved psoriasis inflammation E Martini, M Wiken, S Cheuk, A Smed Sorensen, M Stahle and L Eidsmo Dept. of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden In psoriasis, scaly skin lesions are caused by interactions between activated keratinocytes, T cells and dendritic cells present in the skin. Here we investigate the inflammatory profiles of skin resident Langerhans cells (LCs) and infiltrating epitdermal dendritic cells (eDCs) to determine if they have the potential to steer epithelial pathology in psoriasis. A population of LangerinCD11cCD1c eDCs with variable levels of CD1a and CD14 was strictly confined to epidermis in active psoriasis lesions and could not be detected in non lesional or resolved psoriasis or healthy skin. LCs and eDCs sorted from active psoriasis displayed shared expression of genes associated with T cell activation and neutrophil attraction. Although LCs from psoriatic lesions stimulated with Toll-like receptor (TLR) ligands produced the pro-inflammatory cytokines IL-1 beta and IL-23, eDCs were the major producer of these cytokines in the epidermis, and displayed comparable cytokine production to dDCs. In resolved psoriasis eDCs are absent but LCs promptly responded to TLR stimulation with increased IL-23 production. Our results show that infiltrating eDCs together with LCs strongly contribute to the pro-inflammatory environment within the epidermal compartment of the skin. In contrast, LCs alone show the capacity to activate pathogenic tissue resident T cells in resolved psoriasis.