Suppressive Effect of 1α,25-Dihydroxyvitamin D3 on Th17-Immune Responses in Kidney Transplant Recipients with Tacrolimus-Based Immunosuppression

Background The aim of this study was to investigate whether 1α,25-dihydroxyvitamin D3 can regulate Th17-related immune responses in kidney transplant recipients (KTRs) being treated with tacrolimus (Tac)-based immunosuppression. Methods First, we evaluated the effect of 1α,25-dihydroxyvitamin D3 (1,25(OH) 2 D3) on Th17-immune responses in an in vitro study using peripheral blood mononuclear cells (PBMCs) from healthy volunteers or KTRs. Next, we investigated mammalian target of rapamycin/STAT3 signaling as a mechanism by which 1,25(OH) 2 D3 exerted its effect on T cells using the Jurkat cell line. Third, we investigated Th17-cytokine levels or Th17 cell percentage in PBMCs according to the serum 25-hydroxyvitamin D (25(OH)D) level in 81 KTRs, and we performed a prospective study to assess whether 1,25(OH) 2 D3 (calcitriol) treatment decreased Th17 cytokine levels (IL-17, IL-22) in 42 KTRs. Results In the in vitro study, we observed that the addition of 1,25(OH) 2 D3 to Tac significantly inhibited the appearance of IL-17-positive cells in culture. The expression of IL-17 and IL-22 messenger RNA in PBMCs was also decreased by the addition of 1,25(OH) 2 D3. In the Jurkat cell line, the mTOR/STAT3 pathway was further downregulated with the addition of 1,25(OH) 2 D3 to Tac. In the 81 KTRs, the 25(OH)D level was inversely correlated with the Th17 cytokine levels or the proportion of Th17 cell out of CD4 + T cells. Treatment with calcitriol for 6 months significantly decreased Th17 cytokine levels compared with the baseline values in another 42 KTRs. Conclusions Treatment with 1,25(OH) 2 D3 may have immunologic benefits by effectively suppressing the Th17-related immune responses in KTRs on Tac-based immunosuppression.