1,25-dihydroxyvitamin d3 ameliorates collagen-induced arthritis via suppression of Th17 cells through miR-124 mediated inhibition of IL-6 signaling

Li Zhou, Julie Wang, Jingren Li, Ting Li, Yanming Chen, Rayford R. June, Song Guo Zheng

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Objectives: To explore the molecular mechanisms in which Vitamin D (VD) regulates T cells, especially Th17 cells in collagen-induced arthritis (CIA). Methods: DBA1/J mice induced for CIA were intraperitoneally treated with VD. CIA clinical symptoms and inflammatory responses including Th1/Th17/Tregs percentages were determined and compared. Mouse naïve CD4+ T cells transduced with miR-124 inhibitor or not were polarized to Th17 cells with or without VD. Subsequently, cellular differentiation and IL-6 signaling moleculars were analyzed. Results: VD treatment significantly delayed CIA onset, decreased incidence and clinical scores of arthritis, downregulated serum IgG levels and ameliorated bone erosion. VD downregulated IL-17A production in CD4+ T cells while increased CD4+Foxp3+Nrp-1+ cells both in draining lymph nodes and synovial fluid in arthritic mice. VD inhibited Th17 cells differentiation in vivo and in vitro and potentially functioning directly on T cells to restrain Th17 cells through limiting IL-6R expression and its downstream signaling including STAT3 phosphorylation, while these effects were blocked when naïve CD4+ T cells were transduced with miR-124 inhibitor. Conclusions: VD treatment ameliorates CIA via suppression of Th17 cells and enhancement of Tregs. miR-124-mediated inhibition of IL-6 signaling, provides a novel explanation for VD's role on T cells in CIA mice or RA patients and suggests that VD may have treatment implications in rheumatoid arthritis.

Original languageEnglish (US)
Article number178
JournalFrontiers in immunology
Issue numberFEB
StatePublished - Jan 1 2019


All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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