Differential regulation of Tregs and Th17/Th1 cells by a sirolimus-based regimen might be dependent on STAT-signaling in renal transplant recipients

• Sirolimus treated recipients revealed increased Treg.
• Th17 and Th1 related cytokine were decreased in sirolimus treated recipients.
• Sirolimus treated recipients showed increased STAT5 and decreased STAT3.

BackgroundSirolimus (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.MethodsThe 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.ResultsRenal 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.ConclusionOur results indicate that conversion to SRL might both minimize calcineurin inhibitor toxicity and promote immune tolerance.