Increased miR-223 expression in T cells from patients with rheumatoid arthritis leads to decreased insulin-like growth factor-1-mediated interleukin-10 production

Authors

  • M.-C. Lu,

    1. Division of Allergy, Immunology, and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
    2. School of Medicine, Tzu Chi University, Hualien, Taiwan
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  • C.-L. Yu,

    1. Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
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  • H.-C. Chen,

    1. Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
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  • H.-C. Yu,

    1. Division of Allergy, Immunology, and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
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  • H.-B. Huang,

    1. Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan
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  • N.-S. Lai

    Corresponding author
    1. Division of Allergy, Immunology, and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
    2. School of Medicine, Tzu Chi University, Hualien, Taiwan
    • Correspondence: N.-S. Lai, Division of Allergy, Immunology, and Rheumatology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, no. 2, Minsheng Road, Dalin, Chiayi 62247 Taiwan.

      E-mail: tzuchilai@gmail.com

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Summary

We hypothesized that the aberrant expression of microRNAs (miRNAs) in rheumatoid arthritis (RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T cells from the first five RA patients and five controls were analysed by real-time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR-223 and miR-34b were over-expressed in RA T cells. The expression levels of miR-223 were correlated positively with the titre of rheumatoid factor (RF) in RA patients. Transfection of Jurkat cells with miR-223 mimic suppressed insulin-like growth factor-1 receptor (IGF-1R) and transfection with miR-34b mimic suppressed cAMP response element binding protein (CREB) protein expression by Western blotting. The protein expression of IGF-1R but not CREB was decreased in RA T cells. The addition of recombinant IGF-1-stimulated interleukin (IL)-10 production by activated normal T cells, but not RA T cells. The transfection of miR-223 mimic impaired IGF-1-mediated IL-10 production in activated normal T cells. The expression levels of SCD5, targeted by miR-34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR-223 and miR-34b were over-expressed in RA T cells, but only the miR-223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR-223 expression could impair the IGF-1-mediated IL-10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti-inflammatory cytokines.

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