title: T2 enhances in situ level of Foxp3+ regulatory cells and modulates inflammatory cytokines in Crohn's disease.
abstract: BACKGROUND
  Acting via IL-10 and transforming growth factor-β (TGF-β), t regulatory cells (Tregs) that express the Forkhead Box P3 (Foxp3) play a vital role in maintaining intestinal immune homeostasis. Many studies have found correlation between Foxp3(+) Treg cells and Crohn's disease (CD). T2, extracted from the medicinal plant Tripterygium wilfordii Hook F, has already been proved to be therapeutically effective in inducing the remission of CD. However, the mechanisms in human studies remain largely unknown.
  
  
  OBJECTIVE
  We aimed to explore the effect of T2 on the in situ levels of inflammatory cytokines and the number of Foxp3(+) Tregs in inflamed mucosa of CD.
  
  
  METHODS
  Mucosal biopsies from 20 patients treated with T2 were taken by colonoscopy. The changes of Foxp3(+) Tregs as well as TNF-α and IL-10 in diseased tissue were visualized by immunochemistry. Western blot and ELISA were used to quantify levels of Foxp3 protein expression and inflammatory cytokines.
  
  
  RESULTS
  T2 treatment ameliorated the pathological inflammation of CD. We observed that the significantly elevated Foxp3(+) Tregs and IL-10 levels in the mucosa of CD patients after T2 treatment concurred with the down-regulation of proinflammatory TNF-α.
  
  
  CONCLUSIONS
  We confirmed the efficacy of T2 treatment in CD and showed that microscopic inflammation was attenuated by the modulation of in situ levels of inflammatory cytokines. The therapeutic mechanisms might involve the up-regulation of Foxp3(+) Tregs.
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: li.guanwei@foxmail.com.
authors.forename: Guanwei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: JiananR@gmail.com.
authors.forename: Jianan
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: Wgfwang@gmail.com.
authors.forename: Gefei
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: guguoshengde@163.com.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Gu
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: hdalce@gmail.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: rhj1288@163.com.
authors.forename: Huajian
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: 330181371@qq.com.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Hong
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: lygwxw@163.com.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: medical.lis@gmail.com.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: jieshoulee@sina.com.
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D029757:Tripterygium; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D010616:Phenanthrenes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C001899:triptolide
keywords: Crohn's disease; Regulatory t cells; Tripterygium wilfordii Hook F; Triptolide