1,25(OH)2D3 suppresses proinflammatory responses by inhibiting Th1 cell differentiation and cytokine production through the JAK/STAT pathway.

1,25(OH)2D3 is an immune modulation hormone with beneficial effects on T cell- mediated autoimmune diseases. The purpose of the present study is to investigate the direct effects of vitamin D on Bacillus Calmette Guerin (BCG)-infected CD4+ T cells in both VDR-deficient (VDR-/-) mice and wild type (WT) mice. Specifically, we aimed to investigate the effect of vitamin D on Th1 cells and elucidate the underlying molecular mechanism. Naïve CD4 T cells were purified from VDR-/- mice and WT mice to induce Th1 cells and were activated by BCG. Th1 cell differentiation and cytokine production in vitro were inhibited by 10 nM 1,25(OH)2D3. The JAK/STAT pathway was activated by 1,25(OH)2D3 addition in both VDR-/- and wild type T cells. In vivo, a vitamin D-deficiency VDR-/- and WT mouse model was established and the mice were vaccinated with BCG. An ELISA assay was performed to measure the levels of VD, IL-2, IFN-γ and TNF-β in the blood, and flow cytometry was used to analyze the proportion of Th1 and Th2 cells in the spleen. 1,25(OH)2D3 affected Th cells polarization by inhibiting Th1 and augmenting Th2 cell development in the vitamin D-deficiency mouse model. Moreover, 1,25(OH)2D3 inhibited the inflammatory infiltrates and expression of IL-2, IFN-γ and TNF-β in the spleen of vitamin D-deficient mice following vaccination with BCG. These findings suggested that 1,25(OH)2D3 suppressed the inflammatory response by inhibiting Th1 cell differentiation and cytokine production by the JAK/STAT pathway.