Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis
Journal
Clinical and Experimental Immunology
Journal Volume
173
Journal Issue
1
Pages
47-57
Date Issued
2013
Author(s)
Abstract
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. 2013 British Society for Immunology.
Subjects
Ankylosing spondylitis; Interferon gamma; Let-7i; MicroRNA; T cells; Toll-like receptor-4
SDGs
Other Subjects
C reactive protein; CD28 antigen; CD3 antibody; gamma interferon; HLA B27 antigen; interstitial collagenase; microRNA; microRNA 16; microRNA 221; protein; protein let 7i; toll like receptor 4; unclassified drug; adult; ankylosing spondylitis; article; clinical article; controlled study; disease activity; female; genetic transfection; human; immunopathogenesis; interferon production; leukemia cell line; lumbar spine; male; priority journal; protein degradation; protein expression; sacroiliitis; T lymphocyte; Adult; Arthritis, Rheumatoid; Case-Control Studies; Cells, Cultured; Female; Gene Expression Regulation; Humans; Interferon-gamma; Jurkat Cells; Lipopolysaccharides; Lumbar Vertebrae; Lupus Erythematosus, Systemic; Male; MicroRNAs; Middle Aged; RNA, Messenger; Severity of Illness Index; Spondylitis, Ankylosing; Th1 Cells; Toll-Like Receptor 4; Young Adult
Type
journal article