Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis

Authors

  • N.-S. Lai,

    1. Division of Allergy, Immunology and Rheumatology, Buddhist Dalin Tzu Chi General Hospital, Taiwan
    2. School of Medicine, Tzu Chi University, Hualien, Taiwan
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    • Ning-Sheng Lai and Hui-Chun Yu contributed equally to this study.
  • H.-C. Yu,

    1. Division of Allergy, Immunology and Rheumatology, Buddhist Dalin Tzu Chi General Hospital, Taiwan
    2. Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan
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    • Ning-Sheng Lai and Hui-Chun Yu contributed equally to this study.
  • H.-C. Chen,

    1. Department of Biomedical Sciences, Chang Gung University, Tao-Yuan, 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.-B. Huang,

    1. Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan
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  • M.-C. Lu

    Corresponding author
    1. School of Medicine, Tzu Chi University, Hualien, Taiwan
    • Division of Allergy, Immunology and Rheumatology, Buddhist Dalin Tzu Chi General Hospital, Taiwan
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Correspondence: M.-C. Lu, Division of Allergy, Immunology, and Rheumatology, Buddhist Dalin Tzu Chi General Hospital No. 2, Min-Sheng Road, Dalin Town, Chia-Yi, Taiwan 62247.

E-mail: e360187@yahoo.com.tw

Summary

Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of microRNAs (miRNAs) in AS T cells involved in the pathogenesis of AS. The expression profile of 270 miRNAs in T cells from five AS patients and five healthy controls were analysed by real-time polymerase chain reaction (PCR). Thirteen miRNAs were found potentially differential expression. After validation, we confirmed that miR-16, miR-221 and let-7i were over-expressed in AS T cells and the expression of miR-221 and let-7i were correlated positively with the Bath Ankylosing Spondylitis Radiology Index (BASRI) of lumbar spine in AS patients. The protein molecules regulated by miR-16, miR-221 and let-7i were measured by Western blotting. We found that the protein levels of Toll-like receptor-4 (TLR-4), a target of let-7i, in T cells from AS patients were decreased. In addition, the mRNA expression of interferon (IFN)-γ was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR-4 agonist, inhibited IFN-γ secretion by anti-CD3+anti-CD28 antibodies-stimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let-7i enhanced IFN-γ production by anti-CD3+anti-CD28+ lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-γ production by anti-CD3+anti-CD28+ LPS-stimulated AS T cells. In conclusion, we found that miR-16, miR-221 and let-7i were over-expressed in AS T cells, but only miR-221 and let-7i were associated with BASRI of lumbar spine. In the functional studies, the increased let-7i expression facilitated the T helper type 1 (IFN-γ) immune response in T cells.

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