Increased miR‐223 expression in T cells from patients with rheumatoid arthritis leads to decreased insulin‐like growth factor‐1‐mediated interleukin‐10 production

• Published in: Clinical and experimental immunology Vol. 177; no. 3; pp. 641 - 651
• Main Authors: Lu, M.‐C., Yu, C.‐L., Chen, H.‐C., Yu, H.‐C., Huang, H.‐B., Lai, N.‐S.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-09-2014; Blackwell Science Inc
• Subjects: Adult; Aged; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Case-Control Studies; CD28 Antigens - immunology; CD3 Complex - immunology; Cell Line; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Cytokines; Female; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Humans; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; insulin‐like growth factor‐1 receptor; interleukin 10; Interleukin-10 - biosynthesis; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes; Male; MicroRNAs - genetics; Middle Aged; miR‐223; Original; Protein expression; Proteins; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; Rheumatoid arthritis; RNA Interference; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Transfection; miR-223; insulin-like growth factor-1 receptor; T cells; rheumatoid arthritis; interleukin 10
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12374

Summary
We hypothesized that the aberrant expression of microRNAs (miRNAs) in rheumatoid arthritis (RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T cells from the first five RA patients and five controls were analysed by real‐time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR‐223 and miR‐34b were over‐expressed in RA T cells. The expression levels of miR‐223 were correlated positively with the titre of rheumatoid factor (RF) in RA patients. Transfection of Jurkat cells with miR‐223 mimic suppressed insulin‐like growth factor‐1 receptor (IGF‐1R) and transfection with miR‐34b mimic suppressed cAMP response element binding protein (CREB) protein expression by Western blotting. The protein expression of IGF‐1R but not CREB was decreased in RA T cells. The addition of recombinant IGF‐1‐stimulated interleukin (IL)‐10 production by activated normal T cells, but not RA T cells. The transfection of miR‐223 mimic impaired IGF‐1‐mediated IL‐10 production in activated normal T cells. The expression levels of SCD5, targeted by miR‐34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR‐223 and miR‐34b were over‐expressed in RA T cells, but only the miR‐223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR‐223 expression could impair the IGF‐1‐mediated IL‐10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti‐inflammatory cytokines.