1,25-Dihydroxyvitamin D3 Ameliorates Collagen-Induced Arthritis via Suppression of Th17 Cells Through miR-124 Mediated Inhibition of IL-6 Signaling

Frontiers in Immunology
Li ZhouSong Guo Zheng

Abstract

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 suppres...Continue Reading

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Citations

Jun 14, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Xiaoyan LiTaitao Sun
May 2, 2020·Nutrients·Pieter-Jan MartensAnd Chantal Mathieu
Jul 31, 2020·BMC Rheumatology·Stephanie R HarrisonKarim Raza
Aug 8, 2019·Biomolecules·Lihui XieWenru Su
Jun 2, 2020·Frontiers in Immunology·Zhenkun WangSong Guo Zheng
Jul 20, 2019·Autoimmunity Reviews·Giuseppe MurdacaSebastiano Gangemi
Jan 14, 2021·Biology of Sex Differences·Maria Luisa DupuisElena Ortona
Mar 9, 2021·Frontiers in Immunology·Rui ZhaoSong Guo Zheng
May 11, 2021·Frontiers in Immunology·Junxia HuangJi Yang
Jun 12, 2021·Expert Review of Anti-infective Therapy·Sadaf Jamal GilaniImran Kazmi
Jul 11, 2021·Cancer Prevention Research·Sarah M BernhardtPepper Schedin
Aug 2, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ye ChenSong Guo Zheng

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Methods Mentioned

BETA
ELISA
PMA
flow cytometry
PCR
electrophoresis

Software Mentioned

Amira
FlowJo
GraphPad Prism
Inveon Acquisition Workplace

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