Aberrant expression of micro RNA s in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis

Summary Ankylosing spondylitis ( AS ) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of micro RNA s (mi RNA s) in AS T cells involved in the pathogenesis of AS . The expression profile of 270 mi RNA s in T cells from five AS patients and five healthy controls were analysed by real‐time polymerase chain reaction ( PCR) . Thirteen mi RNA s were found potentially differential expression. After validation, we confirmed that mi R ‐16, mi R ‐221 and let‐7i were over‐expressed in AS T cells and the expression of mi R ‐221 and let‐7i were correlated positively with the B ath A nkylosing S pondylitis R adiology I ndex ( BASRI ) of lumbar spine in AS patients. The protein molecules regulated by mi R ‐16, mi R ‐221 and let‐7i were measured by W estern blotting. We found that the protein levels of T oll‐like receptor‐4 ( TLR‐ 4), a target of let‐7i, in T cells from AS patients were decreased. In addition, the m RNA expression of interferon ( IFN) ‐γ was elevated in AS T cells. Lipopolysaccharide ( LPS ), a TLR‐ 4 agonist, inhibited IFN ‐γ secretion by anti‐ CD 3 + anti‐ CD 28 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‐ CD 3 + anti‐ CD 28 + lipopolysaccharide (LPS) ‐stimulated normal T cells. In contrast, the decreased expression of let‐7i suppressed IFN ‐γ production by anti‐ CD 3 + anti‐ CD 28 + LPS ‐stimulated AS T cells. In conclusion, we found that mi R ‐16, mi R ‐221 and let‐7i were over‐expressed in AS T cells, but only mi R ‐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.