title: Differential regulation of Tregs and Th17/Th1 cells by a sirolimus-based regimen might be dependent on STAT-signaling in renal transplant recipients.
abstract: BACKGROUND
  Sirolimus (SRL), a mammalian target of rapamycin inhibitor, has been used as a de novo base therapy with steroids and mycophenolate mofetil to avoid the use of calcineurin inhibitors. Our aim was to determine whether immunoregulation is promoted after conversion from tacrolimus (TAC) to SRL.
  
  
  METHODS
  The study included 24 renal transplant recipients who converted from TAC to SRL therapy and 24 normal controls. The frequency of T helper (Th) cells and the presence of signal transducer and activator of transcription (STAT) proteins in peripheral blood were analyzed by flow cytometry before conversion and at 3 and 6 months after conversion. Plasma levels of interleukin (IL)-1β, interferon-γ (IFN-γ), IL-17, IL-6, and IL-10 were analyzed by the Bio-Plex® suspension array system before and at 3 months after conversion.
  
  
  RESULTS
  Renal transplant recipients who switched to SRL showed a significant increase in regulatory T cell (Treg) frequencies and better renal function compared with preconversion (P<0.05). The plasma concentrations of inflammatory cytokines IL-1β, IL-6, IL-17, and IFN-γ were significantly decreased after conversion to SRL. Furthermore, recipients who switched to SRL showed an increase in STAT5 activation and a decrease in STAT3 activation compared with the TAC group.
  
  
  CONCLUSIONS
  Our results indicate that conversion to SRL might both minimize calcineurin inhibitor toxicity and promote immune tolerance.
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yunying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: wanglanlan89@126.com.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016559:Tacrolimus / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus
keywords: Calcineurin inhibitors; Regulatory T cells; Renal transplantation; Sirolimus; Stat proteins; Th17 cells