title: Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis.
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.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Buddhist Dalin Tzu Chi General Hospital, Taiwan.
authors.forename: N-S
authors.initials: NS
authors.lastname: Lai
authors.forename: H-C
authors.initials: HC
authors.lastname: Yu
authors.forename: H-C
authors.initials: HC
authors.lastname: Chen
authors.forename: C-L
authors.initials: CL
authors.lastname: Yu
authors.forename: H-B
authors.initials: HB
authors.lastname: Huang
authors.forename: M-C
authors.initials: MC
authors.lastname: Lu
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D011859:Radiography; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: D007371:Interferon-gamma; D008070:Lipopolysaccharides; D035683:MicroRNAs; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; C505362:MIRN16 microRNA, human; C525709:MIR221, human; C495345:TLR4 protein, human; C487931:mirnlet7 microRNA, human