F F Wang1,2, Y Wang2, L Wang2, T S Wang3, Y P Bai2. 1. Graduate School, Beijing University of Chinese Medicine, Beijing, China. 2. Department of Dermatology and Venereology, China-Japan Friendship Hospital, Beijing, China. 3. Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Abstract
BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT), a co-inhibitory receptor, suppresses CD4+ T-cell responses by triggering CD155. TIGIT shifts the balance of cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, and affects the proliferation of CD4+ T cells. AIM: To investigate TIGIT expression and its effects on CD4+ T-cell function in psoriasis. METHODS: In total, 28 patients with psoriasis vulgaris PV and 14 healthy controls (HCs) were enrolled. TIGIT expression on CD4+ T cells was evaluated by flow cytometry analysis and quantitative real-time PCR. Production of IFN-γ, IL-10 and IL-17 was measured with cytometry bead arrays, while CD4+ T cell proliferation was measured using a permeable assay. RESULTS: IGIT expression on CD4+ T cells and mRNA level were significantly lower in patients with PV compared with HCs. TIGIT expression was negatively correlated with Psoriasis Area and Severity Index. Activation of TIGIT with recombinant human CD155/Fc protein significantly inhibited psoriatic CD4+ T-cell proliferation, decreased production of IFN-γ and IL-17A, and increased IL-10. After blockade with a functional anti-human TIGIT antibody, TIGIT produced the opposite effect on IFN-γ and IL-17A, but had no significant effect on IL-10 or cell proliferation. Furthermore, the frequency of TIGIT+CD4+ T cells was significantly increased in patients with PV after 2 months of treatment with acitretin, with associated significant changes in IFN-γ, IL-10and IL-17A plasma levels. CONCLUSIONS: Downregulation of TIGIT on CD4+ T cells may contribute to the pathogenesis of psoriasis, and activation of the TIGIT signalling pathway may be a potential therapeutic target.
BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT), a co-inhibitory receptor, suppresses CD4+ T-cell responses by triggering CD155. TIGIT shifts the balance of cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, and affects the proliferation of CD4+ T cells. AIM: To investigate TIGIT expression and its effects on CD4+ T-cell function in psoriasis. METHODS: In total, 28 patients with psoriasis vulgaris PV and 14 healthy controls (HCs) were enrolled. TIGIT expression on CD4+ T cells was evaluated by flow cytometry analysis and quantitative real-time PCR. Production of IFN-γ, IL-10 and IL-17 was measured with cytometry bead arrays, while CD4+ T cell proliferation was measured using a permeable assay. RESULTS: IGIT expression on CD4+ T cells and mRNA level were significantly lower in patients with PV compared with HCs. TIGIT expression was negatively correlated with Psoriasis Area and Severity Index. Activation of TIGIT with recombinant humanCD155/Fc protein significantly inhibited psoriatic CD4+ T-cell proliferation, decreased production of IFN-γ and IL-17A, and increased IL-10. After blockade with a functional anti-human TIGIT antibody, TIGIT produced the opposite effect on IFN-γ and IL-17A, but had no significant effect on IL-10 or cell proliferation. Furthermore, the frequency of TIGIT+CD4+ T cells was significantly increased in patients with PV after 2 months of treatment with acitretin, with associated significant changes in IFN-γ, IL-10and IL-17A plasma levels. CONCLUSIONS: Downregulation of TIGIT on CD4+ T cells may contribute to the pathogenesis of psoriasis, and activation of the TIGIT signalling pathway may be a potential therapeutic target.
Authors: YoungHwan Choi; Donghwi Jang; Hyun Jeong Byun; Se Jin Oh; Cho Rok Kim; Ji-Hye Park; Jong Hee Lee; Dong-Youn Lee Journal: Ann Dermatol Date: 2020-03-11 Impact factor: 1.444
Authors: Dennis Niebel; Anne Fröhlich; Jennifer Landsberg; Dimo Dietrich; Romina Zarbl; Simon Fietz; Luka de Vos; Timo J Vogt; Jörn Dietrich; Judith Sirokay; Pia Kuster; Gonzalo Saavedra; Susana Ramírez Valladolid; Friederike Hoffmann; Sebastian Strieth Journal: Clin Epigenetics Date: 2022-04-11 Impact factor: 6.551