M Mattii1, M Lovászi2, N Garzorz3, A Atenhan1, M Quaranta1, F Lauffer3, A Konstantinow3, M Küpper1, C C Zouboulis4, L Kemeny5, K Eyerich3, C B Schmidt-Weber1, D Törőcsik2, S Eyerich1. 1. ZAUM - Center for Allergy and Environment, Technische Universität and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Biedersteinerstraße 29, 80802, Munich, Germany. 2. Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 3. Department of Dermatology and Allergy, Technische Universität Munich, Munich, Germany. 4. Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany. 5. Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary.
Abstract
BACKGROUND: The main function of sebocytes is considered to be the production of lipids to moisturize the skin. However, it recently became apparent that sebocytes release chemokines and cytokines and respond to proinflammatory stimuli as well as the presence of bacteria. OBJECTIVES: To analyse the functional communication between human sebocytes and T cells. METHODS: Immunofluorescence stainings for CD4 and interleukin (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 prestimulated SZ95 sebocytes. Dendritic cells were generated in the presence of SZ95 supernatant and subsequently used in mixed leucocyte reactions. RESULTS: We showed 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 CXCL8-dependent manner. Furthermore, sebocyte supernatant induces the differentiation of CD4+ CD45RA+ naive T cells into T helper (Th)17 cells via the secretion of IL-6, transforming growth factor-β and, most importantly, IL-1β. 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, which might contribute to the pathogenesis not only of acne vulgaris, but also of several inflammatory skin diseases.
BACKGROUND: The main function of sebocytes is considered to be the production of lipids to moisturize the skin. However, it recently became apparent that sebocytes release chemokines and cytokines and respond to proinflammatory stimuli as well as the presence of bacteria. OBJECTIVES: To analyse the functional communication between human sebocytes and T cells. METHODS: Immunofluorescence stainings for CD4 and interleukin (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 prestimulated SZ95 sebocytes. Dendritic cells were generated in the presence of SZ95 supernatant and subsequently used in mixed leucocyte reactions. RESULTS: We showed 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 CXCL8-dependent manner. Furthermore, sebocyte supernatant induces the differentiation of CD4+ CD45RA+ naive T cells into T helper (Th)17 cells via the secretion of IL-6, transforming growth factor-β and, most importantly, IL-1β. 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, which might contribute to the pathogenesis not only of acne vulgaris, but also of several inflammatory skin diseases.
Authors: Arnold Markovics; Kinga Fanni Tóth; Katalin Eszter Sós; József Magi; Adrienn Gyöngyösi; Zoltán Benyó; Christos C Zouboulis; Tamás Bíró; Attila Oláh Journal: J Cell Mol Med Date: 2019-07-05 Impact factor: 5.310
Authors: Bénédicte Oulès; Christina Philippeos; Joe Segal; Matthieu Tihy; Matteo Vietri Rudan; Ana-Maria Cujba; Philippe A Grange; Sven Quist; Ken Natsuga; Lydia Deschamps; Nicolas Dupin; Giacomo Donati; Fiona M Watt Journal: Nat Commun Date: 2020-10-20 Impact factor: 14.919