title: Impaired function of regulatory T cells in patients with psoriasis is mediated by phosphorylation of STAT3.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Luting
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Erle
authors.initials: E
authors.lastname: Dang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: xjwgang@fmmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010766:Phosphorylation; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Pro-inflammatory cytokines; Psoriasis; Regulatory T cells; STAT3