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


Lai N-S12,Yu H-C13,Chen H-C4,Yu C-L5,Huang H-B3,Lu M-C12


1. Division of Allergy, Immunology and Rheumatology, Buddhist Dalin Tzu Chi General Hospital, Taiwan

2. School of Medicine, Tzu Chi University, Hualien, Taiwan

3. Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan

4. Department of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan

5. Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan


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.


National Science Council

Buddhist Dalin Tzu-Chi General Hospital, Taiwan


Oxford University Press (OUP)


Immunology,Immunology and Allergy








Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3