MicroRNAs (miRNAs) function to fine‐tune the control of immune cell signaling. It is well established that there are abnormalities in the interleukin‐2 (IL‐2)–related signaling pathways in systemic lupus erythematosus (SLE). The miR‐31 microRNA has been found to be markedly underexpressed in patients with SLE, and thus the present study was undertaken to investigate the role of miR‐31 in IL‐2 defects in lupus T cells.

Expression levels of miR‐31 were quantitated using TaqMan miRNA assays. Transfection and stimulation of cultured cells followed by TaqMan quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, and reporter gene assays were conducted to determine the biologic function of miR‐31. NF‐AT nuclear translocation and expression were quantitatively measured using an ImageStream cytometer. Bioinformatics analysis, small interfering RNA (siRNA) knockdown, and Western blotting were performed to validate miR‐31 targets and effects.

The expression of miR‐31 was significantly decreased in lupus T cells, and this was positively correlated with the expression of IL‐2. Overexpression of miR‐31 in T cells increased the production of IL‐2 by altering NF‐AT nuclear expression and IL2 promoter activity, while knockdown of endogenous miR‐31 reduced IL‐2 production. RhoA expression was directly repressed by miR‐31 in T cells. Of note, siRNA‐mediated knockdown of RhoA enhanced IL2 promoter activity and, consequently, up‐regulated IL‐2 production. RhoA expression was consistently up‐regulated and negatively correlated with the levels of miR‐31 in lupus T cells. Manipulation of miR‐31 expression in lupus T cells restored the expression of IL‐2 at both the messenger RNA and protein levels.

MicroRNA‐31 is a novel enhancer of IL‐2 production during T cell activation. Dysregulation of miR‐31 and its target, RhoA, could be a novel molecular mechanism underlying the IL‐2 deficiency in patients with SLE.