Sebocytes contribute to skin inflammation by promoting the differentiation of Th17 cells

BACKGROUND: The main function of sebocytes is considered to be the lipid production for moisturizing the skin. However, it became recently apparent that sebocytes release chemokines and cytokines and respond to pro-inflammatory stimuli as well as presence of bacteria. OBJECTIVES: To analyze the functional communication between human sebocytes and T cells. METHODS: Immunofluorescence stainings for CD4 and IL-17 were performed on acne sections and healthy skin. Migration assays and T cell stimulation cultures were performed with supernatants derived from unstimulated or pre-stimulated SZ95 sebocytes. DCs were generated in presence of SZ95 supernatant and subsequently used in mixed leukocyte reactions. RESULTS: We could show that CD4+IL-17+ T cells accumulate around the pilosebaceous unit and are in close contact with sebocytes in acne lesions. By using SZ95 sebocyte supernatant, we demonstrate a chemotactic effect of sebocytes on neutrophils, monocytes and T cells in a CXCL-8 dependent manner. Furthermore, sebocyte supernatant induces the differentiation of CD4+ CD45RA+ naive T cells into Th17 cells via the secretion of IL-6, TGF-beta and, most importantly, IL-1beta. No direct effects of sebocytes on the function of CD4+ CD45RO+ memory T cells were detected. Moreover, sebocytes functionally interact with Propionibacterium acnes in the maturation of dendritic cells leading to antigen presenting cells that preferentially prime Th17 cells. CONCLUSIONS: Our study provides evidence that human sebocytes actively participate in inflammatory processes in the skin by recruiting and communicating with immune cells. This interaction leads to the generation of Th17 cells that might contribute not only to the pathogenesis of acne vulgaris, but to several inflammatory skin diseases. This article is protected by copyright. All rights reserved