Correcting the expression of miRNA-155 represses PP2Ac and enhances the release of IL-2 in PBMCs of juvenile SLE patients.

[familial mediterranean fever]

MicroRNA-155 is involved in immune cell , differentiation , maturation and function . MiR-155 showed variable dysregulated expression in autoimmune diseases such as systemic lupus erythematosus (SLE ) and rheumatoid arthritis (RA ) patients . MiR-155 was previously confirmed to directly target CAMP response element binding protein (CREB ), which was previously identified as a positive regulator of protein phosphatase 2 A (PP 2 A ). PP 2 A is a key negative regulator of interleukin-2 , which is an important immune modulator and was previously shown to be decreased in SLE . In this study we aimed at investigating the regulation of PP 2 A by miR-155 and hence its role in juvenile SLE disease pathogenesis . MiR-155 showed significant downregulation in PBMCs from juvenile SLE and juvenile familial Mediterranean fever (FMF ) and significant upregulation in PBMCs from juvenile idiopathic arthritis (JIA ) patients . In SLE , miR-155 expression was negatively correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI ) score and proteinuria and was positively correlated with white blood cell (WBC ) count . The mRNA of the catalytic subunit of PP 2 A (PP 2 A c ) showed significant upregulation in PBMCs from SLE and FMF but not in JIA patients . Additionally , the relative expression of PP 2 Ac mRNA was positively correlated with SLEDAI score . Forced expression of miR-155 led to decreased relative expression of PP 2 Ac mRNA and increased IL -2 release in cultured-stimulated PBMCs . This study suggests for the first time the possible role of an miR-155 -PP 2 Ac loop in regulating IL -2 release and identifies miR-155 as a potential therapeutic target in juvenile SLE disease through relieving IL -2 from the inhibitory role of PP 2 A .