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

Clin Exp Immunol. 2013 Jul;173(1):47-57. doi: 10.1111/cei.12089.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / metabolism
  • Case-Control Studies
  • Cells, Cultured / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Jurkat Cells / metabolism
  • Lipopolysaccharides / pharmacology
  • Lumbar Vertebrae / diagnostic imaging
  • Lupus Erythematosus, Systemic / metabolism
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • MicroRNAs / physiology
  • Middle Aged
  • RNA, Messenger / biosynthesis
  • Radiography
  • Severity of Illness Index
  • Spondylitis, Ankylosing / diagnostic imaging
  • Spondylitis, Ankylosing / etiology
  • Spondylitis, Ankylosing / genetics
  • Spondylitis, Ankylosing / immunology*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Toll-Like Receptor 4 / biosynthesis
  • Toll-Like Receptor 4 / genetics
  • Young Adult


  • Lipopolysaccharides
  • MIRN16 microRNA, human
  • MIRN221 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • mirnlet7 microRNA, human
  • Interferon-gamma