Objective To determine the mechanism by which 1,25-dihydroxyvitamin D3(VD3)regulates the Th17/Treg cell balance to improve sepsis-induced acute kidney injury(AKI).Methods C57BL/6 mice were assigned to a sham operation group(sham group),a sepsis group(CLP group),a VD3 group,a VD3+knockdown control group(VD3+sh-NC group),and a VD3+NLRP6 knockdown group(VD3+sh-NLRP6 group)(n=10 per group).A mouse model of sepsis-induced AKI was established by cecal ligation and puncture(CLP).Hematoxylin and eosin staining was used to observe pathological damage to renal tissue.ELISA was used to detect the serum creatinine(sCr),kidney injury molecule 1(KIM-1),interleukin(IL)-17,and IL-10 levels.Flow cytometry was used to determine the Th17 cell and Treg cell numbers in peripheral blood.Western blotting was used to detect the expression of vitamin D receptor(VDR)and NLRP6 pro-teins in renal tissue.Results Administration of VD3 alleviated the pathological kidney damage in CLP mice,reduced the sCr,KIM-1,and IL-17 levels and the proportion of Th 17 cells in peripheral blood.It also increased the proportion of Treg cells and the IL-10 level,and upregulated the expression of VDR and NLRP6 proteins.Knockdown of NLRP6 reversed the effect of VD3on the Th17/Treg cell imbal-ance and its renoprotective effects in CLP mice.Conclusion VD3 exerts protective effects in sepsis-induced AKI.Its mechanism likely involves the activation of VDR,leading to subsequent upregulation of NLRP6 expression,ultimately improving the Th17/Treg cell imba-lance.

Objective To determine the mechanism by which 1,25-dihydroxyvitamin D3(VD3)regulates the Th17/Treg cell balance to improve sepsis-induced acute kidney injury(AKI).Methods C57BL/6 mice were assigned to a sham operation group(sham group),a sepsis group(CLP group),a VD3 group,a VD3+knockdown control group(VD3+sh-NC group),and a VD3+NLRP6 knockdown group(VD3+sh-NLRP6 group)(n=10 per group).A mouse model of sepsis-induced AKI was established by cecal ligation and puncture(CLP).Hematoxylin and eosin staining was used to observe pathological damage to renal tissue.ELISA was used to detect the serum creatinine(sCr),kidney injury molecule 1(KIM-1),interleukin(IL)-17,and IL-10 levels.Flow cytometry was used to determine the Th17 cell and Treg cell numbers in peripheral blood.Western blotting was used to detect the expression of vitamin D receptor(VDR)and NLRP6 pro-teins in renal tissue.Results Administration of VD3 alleviated the pathological kidney damage in CLP mice,reduced the sCr,KIM-1,and IL-17 levels and the proportion of Th 17 cells in peripheral blood.It also increased the proportion of Treg cells and the IL-10 level,and upregulated the expression of VDR and NLRP6 proteins.Knockdown of NLRP6 reversed the effect of VD3on the Th17/Treg cell imbal-ance and its renoprotective effects in CLP mice.Conclusion VD3 exerts protective effects in sepsis-induced AKI.Its mechanism likely involves the activation of VDR,leading to subsequent upregulation of NLRP6 expression,ultimately improving the Th17/Treg cell imba-lance.