Luting Yang1, Bing Li1, Erle Dang1, Liang Jin1, Xueli Fan1, Gang Wang2. 1. Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. 2. Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: xjwgang@fmmu.edu.cn.
Abstract
BACKGROUND: Psoriasis is a T cell-mediated chronic inflammatory skin disease. Regulatory T cells (Tregs) are crucial in suppressing immune response to maintain the immune balance. Wheras Tregs from psoriatic patients showed poorly activity in suppressing activation of responder T cells (Tresp), the mechanisms involved in this process are still unknown. OBJECTIVES: In this study, we investigated the possible role of STAT3 pathway in the pathogenesis of dysfunctional Tregs in psoriasis. METHODS: The suppressive function and the proliferative activity of Tregs were detected from psoriatic patients and normal healthy controls. Expression of phospho-STAT3 in psoriatic Tregs was evaluated by flow cytometry and immunofluorescence. Furthermore, Tregs were treated with Stattic V (STAT3 inhibitor) in order to investigate the role of STAT3 pathway in the function of Tregs. In addition, IL-6, IL-21 and IL-23 treatments were performed to identify the upstream molecules of STAT3 pathway in Tregs. RESULTS: Tregs from peripheral blood of psoriatic patients showed decreased suppressive function, together with phosphorylation of STAT3. In addition, Tregs isolated from psoriatic patients could produce IFN-γ, TNF-α and IL-17. In the co-culture system of Tregs and Tresp isolated from psoriatic patients, addition of STAT3 inhibitor partially restored the suppressive function of Tregs and restrained the expressions of IFN-γ, TNF-α and IL-17 in psoriatic patients. Moreover, we found that IL-6, IL-21 and IL-23 induced the phosphorylation of STAT3 in Tregs. CONCLUSIONS: Our findings suggest that psoriatic Tregs experience a predominant STAT3 phosphorylation by exposure to pro-inflammatory cytokines, leading to their impaired functions in suppressing Tresp activation.
BACKGROUND:Psoriasis is a T cell-mediated chronic inflammatory skin disease. Regulatory T cells (Tregs) are crucial in suppressing immune response to maintain the immune balance. Wheras Tregs from psoriaticpatients showed poorly activity in suppressing activation of responder T cells (Tresp), the mechanisms involved in this process are still unknown. OBJECTIVES: In this study, we investigated the possible role of STAT3 pathway in the pathogenesis of dysfunctional Tregs in psoriasis. METHODS: The suppressive function and the proliferative activity of Tregs were detected from psoriaticpatients and normal healthy controls. Expression of phospho-STAT3 in psoriatic Tregs was evaluated by flow cytometry and immunofluorescence. Furthermore, Tregs were treated with Stattic V (STAT3 inhibitor) in order to investigate the role of STAT3 pathway in the function of Tregs. In addition, IL-6, IL-21 and IL-23 treatments were performed to identify the upstream molecules of STAT3 pathway in Tregs. RESULTS: Tregs from peripheral blood of psoriaticpatients showed decreased suppressive function, together with phosphorylation of STAT3. In addition, Tregs isolated from psoriaticpatients could produce IFN-γ, TNF-α and IL-17. In the co-culture system of Tregs and Tresp isolated from psoriaticpatients, addition of STAT3 inhibitor partially restored the suppressive function of Tregs and restrained the expressions of IFN-γ, TNF-α and IL-17 in psoriaticpatients. Moreover, we found that IL-6, IL-21 and IL-23 induced the phosphorylation of STAT3 in Tregs. CONCLUSIONS: Our findings suggest that psoriatic Tregs experience a predominant STAT3 phosphorylation by exposure to pro-inflammatory cytokines, leading to their impaired functions in suppressing Tresp activation.
Authors: David M Woods; Rupal Ramakrishnan; Andressa S Laino; Anders Berglund; Kelly Walton; Brian C Betts; Jeffrey S Weber Journal: Clin Cancer Res Date: 2018-08-21 Impact factor: 12.531
Authors: Ian A Myles; Erik D Anderson; Noah J Earland; Kol A Zarember; Inka Sastalla; Kelli W Williams; Portia Gough; Ian N Moore; Sundar Ganesan; Cedar J Fowler; Arian Laurence; Mary Garofalo; Douglas B Kuhns; Mark D Kieh; Arhum Saleem; Pamela A Welch; Dirk A Darnell; John I Gallin; Alexandra F Freeman; Steven M Holland; Sandip K Datta Journal: J Clin Invest Date: 2018-07-23 Impact factor: 14.808