1,25-(OH)₂D₃/Vitamin D receptor alleviates systemic lupus erythematosus by downregulating Skp2 and upregulating p27

Recent evidence has suggested that the 1,25(OH)₂D₃/Vitamin D receptor (VDR) acts to suppress the immune response associated with systemic lupus erythematosus (SLE), a serious multisystem autoimmune disease. Hence, the aim of the current study was to investigate the mechanism by which 1,25-(OH)₂D₃/VDR influences SLE through regulating the Skp2/p27 signaling pathway.

Initially, the levels of 1,25(OH)₂D₃, VDR, Skp2, and p27 were measured in collected renal tissues and peripheral blood. Meanwhile, the levels of inflammatory factors, biochemical indicators (BUN, Cr, anti-nRNP IgG, anti-dsDNA IgG) and urinary protein levels were assayed in in VDRinsert and VDR-knockout mice in response to 1,25(OH)₂D₃ supplement. In addition, the distribution of splenic immune cells was observed in these mice.

Among the SLE patients, the levels of 1,25(OH)₂D₃, VDR and p27 were reduced, while the levels of Skp2 were elevated. In addition, the levels of anti-nRNP IgG and anti-dsDNA IgG were increased, suggesting induction of inflammatory responses. Notably, 1,25(OH)₂D₃/VDR mice had lower concentrations of BUN and Cr, urinary protein levels, precipitation intensity of the immune complex and complement, as well as the levels of anti-nRNP IgG and anti-dsDNA IgG in SLE mice. Additionally, 1,25(OH)₂D₃ or VDR reduced the degree of the inflammatory response while acting to regulate the distribution of splenic immune cells.

This study indicated that 1,25-(OH)₂D₃/VDR facilitated the recovery of SLE by downregulating Skp2 and upregulating p27 expression, suggesting the potential of 1,25-(OH)₂D₃/VDR as a promising target for SLE treatment.