Impaired function of regulatory T cells in patients with psoriasis is mediated by phosphorylation of STAT3. Issue 2 (February 2016)

• Record Type: Journal Article
• Authors: Yang, Luting; Li, Bing; Dang, Erle; Jin, Liang; Fan, Xueli; Wang, Gang
• Is Part Of: Journal of dermatological science. Volume 81:Issue 2(2016:Feb.)
• Page Start: 85
• Page End: 92
• Publication Date: 2016-02
• Subjects: Psoriasis -- Regulatory T cells -- STAT3 -- Pro-inflammatory cytokines; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2015.11.007
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: Tregs from psoriatic patients showed poorly activity in their suppressive and proliferative functions. Phospho-STAT3 was up-regulated in the peripheral blood of psoriatic Tregs. Inhibitor of STAT3 pathway partially restored suppressive function of psoriatic Tregs and restrained the high release of pro-inflammatory cytokines. IL-6, IL-21 and IL-23 induced STAT3 phosphorylation in Tregs. 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.