J Renne1, V Schäfer, T Werfel, M Wittmann. 1. Department of Dermatology, Hannover Medical School, Ricklinger Str. 5, D-30449 Hannover, Germany. renne.julius@mh-hannover.de
Abstract
BACKGROUND: Chronic inflammatory skin diseases such as atopic dermatitis and psoriasis are characterized by the infiltration of lymphocytes into the epidermal compartment. Several studies point to an active role of skin epithelial cells in the pathophysiology of such diseases. OBJECTIVES: In this study we addressed the regulatory function of primary human keratinocytes in the interaction with autologous T cells and monocytes. METHODS: We used a human coculture model with keratinocytes grown from epidermal stem cells of the outer root sheath of human hair follicles and autologous T cells. RESULTS: In our coculture system we observed a high production of interferon (IFN)-γ, but not Th2 cytokines, in the presence of superantigen or antigen-pulsed autologous monocytes. Critical parameters for this effect were: (i) T-cell receptor activation, (ii) an intercellular adhesion molecule-1/lymphocyte function-associated antigen (LFA)-1-dependent interaction between keratinocytes and T cells, and (iii) secretion of interleukin (IL)-1β. Remarkably, in the presence of activated T cells, epithelial cells seemed to be a more significant source of IL-1β than monocytes. Application of the LFA-1 blocker efalizumab or IL-1 receptor antagonist anakinra enabled us to suppress completely the production of IFN-γ by T cells in the coculture. CONCLUSIONS: IL-1 secretion and the physical contact between keratinocytes and activated, infiltrating T cells may be central for the development of chronic inflammatory skin conditions.
BACKGROUND: Chronic inflammatory skin diseases such as atopic dermatitis and psoriasis are characterized by the infiltration of lymphocytes into the epidermal compartment. Several studies point to an active role of skin epithelial cells in the pathophysiology of such diseases. OBJECTIVES: In this study we addressed the regulatory function of primary human keratinocytes in the interaction with autologous T cells and monocytes. METHODS: We used a human coculture model with keratinocytes grown from epidermal stem cells of the outer root sheath of human hair follicles and autologous T cells. RESULTS: In our coculture system we observed a high production of interferon (IFN)-γ, but not Th2 cytokines, in the presence of superantigen or antigen-pulsed autologous monocytes. Critical parameters for this effect were: (i) T-cell receptor activation, (ii) an intercellular adhesion molecule-1/lymphocyte function-associated antigen (LFA)-1-dependent interaction between keratinocytes and T cells, and (iii) secretion of interleukin (IL)-1β. Remarkably, in the presence of activated T cells, epithelial cells seemed to be a more significant source of IL-1β than monocytes. Application of the LFA-1 blocker efalizumab or IL-1 receptor antagonist anakinra enabled us to suppress completely the production of IFN-γ by T cells in the coculture. CONCLUSIONS: IL-1 secretion and the physical contact between keratinocytes and activated, infiltrating T cells may be central for the development of chronic inflammatory skin conditions.
Authors: Ellen H van den Bogaard; Geuranne S Tjabringa; Irma Joosten; Mieke Vonk-Bergers; Esther van Rijssen; Henk J Tijssen; Mirthe Erkens; Joost Schalkwijk; Hans J P M Koenen Journal: J Invest Dermatol Date: 2013-10-11 Impact factor: 8.551
Authors: Yvonne Dombrowski; Mark Peric; Sarah Koglin; Claudia Kammerbauer; Christine Göss; David Anz; Maren Simanski; Regine Gläser; Jürgen Harder; Veit Hornung; Richard L Gallo; Thomas Ruzicka; Robert Besch; Jürgen Schauber Journal: Sci Transl Med Date: 2011-05-11 Impact factor: 17.956
Authors: Yihua Cai; Feng Xue; Chen Quan; Minye Qu; Na Liu; Yuan Zhang; Chris Fleming; Xiaoling Hu; Huang-Ge Zhang; Ralph Weichselbaum; Yang-Xin Fu; David Tieri; Eric C Rouchka; Jie Zheng; Jun Yan Journal: J Invest Dermatol Date: 2018-08-16 Impact factor: 8.551
Authors: Jennifer Nguyen; Richard Bernert; Kevin In; Paul Kang; Noemi Sebastiao; Chengcheng Hu; K Taraszka Hastings Journal: Melanoma Res Date: 2016-04 Impact factor: 3.599