PMID- 23607629 OWN - NLM STAT- MEDLINE DCOM- 20130805 LR - 20220317 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 173 IP - 1 DP - 2013 Jul TI - Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis. PG - 47-57 LID - 10.1111/cei.12089 [doi] AB - 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)-gamma was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR-4 agonist, inhibited IFN-gamma 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-gamma production by anti-CD3(+) anti-CD28(+) lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-gamma 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-gamma) immune response in T cells. CI - (c) 2013 British Society for Immunology. FAU - Lai, N-S AU - Lai NS AD - Division of Allergy, Immunology and Rheumatology, Buddhist Dalin Tzu Chi General Hospital, Taiwan. FAU - Yu, H-C AU - Yu HC FAU - Chen, H-C AU - Chen HC FAU - Yu, C-L AU - Yu CL FAU - Huang, H-B AU - Huang HB FAU - Lu, M-C AU - Lu MC LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Lipopolysaccharides) RN - 0 (MIRN16 microRNA, human) RN - 0 (MIRN221 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (mirnlet7 microRNA, human) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Arthritis, Rheumatoid/metabolism MH - Case-Control Studies MH - Cells, Cultured/metabolism MH - Female MH - Gene Expression Regulation MH - Humans MH - Interferon-gamma/biosynthesis/genetics/metabolism MH - Jurkat Cells/metabolism MH - Lipopolysaccharides/pharmacology MH - Lumbar Vertebrae/diagnostic imaging MH - Lupus Erythematosus, Systemic/metabolism MH - Male MH - MicroRNAs/antagonists & inhibitors/*biosynthesis/genetics/physiology MH - Middle Aged MH - RNA, Messenger/biosynthesis MH - Radiography MH - Severity of Illness Index MH - Spondylitis, Ankylosing/diagnostic imaging/etiology/genetics/*immunology MH - Th1 Cells/immunology/*metabolism MH - Toll-Like Receptor 4/biosynthesis/genetics MH - Young Adult PMC - PMC3694534 EDAT- 2013/04/24 06:00 MHDA- 2013/08/06 06:00 PMCR- 2014/07/01 CRDT- 2013/04/24 06:00 PHST- 2013/02/04 00:00 [accepted] PHST- 2013/04/24 06:00 [entrez] PHST- 2013/04/24 06:00 [pubmed] PHST- 2013/08/06 06:00 [medline] PHST- 2014/07/01 00:00 [pmc-release] AID - 10.1111/cei.12089 [doi] PST - ppublish SO - Clin Exp Immunol. 2013 Jul;173(1):47-57. doi: 10.1111/cei.12089.