{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T06:55:30Z","timestamp":1784357730841,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,10,27]],"date-time":"2012-10-27T00:00:00Z","timestamp":1351296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>MicroRNAs (miRNAs) function to fine\u2010tune the control of immune cell signaling. It is well established that there are abnormalities in the interleukin\u20102 (IL\u20102)\u2013related signaling pathways in systemic lupus erythematosus (SLE). The miR\u201031 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\u201031 in IL\u20102 defects in lupus T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression levels of miR\u201031 were quantitated using TaqMan miRNA assays. Transfection and stimulation of cultured cells followed by TaqMan quantitative polymerase chain reaction, enzyme\u2010linked immunosorbent assay, and reporter gene assays were conducted to determine the biologic function of miR\u201031. NF\u2010AT 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\u201031 targets and effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of miR\u201031 was significantly decreased in lupus T cells, and this was positively correlated with the expression of IL\u20102. Overexpression of miR\u201031 in T cells increased the production of IL\u20102 by altering NF\u2010AT nuclear expression and <jats:italic>IL2<\/jats:italic> promoter activity, while knockdown of endogenous miR\u201031 reduced IL\u20102 production. RhoA expression was directly repressed by miR\u201031 in T cells. Of note, siRNA\u2010mediated knockdown of <jats:italic>RhoA<\/jats:italic> enhanced <jats:italic>IL2<\/jats:italic> promoter activity and, consequently, up\u2010regulated IL\u20102 production. RhoA expression was consistently up\u2010regulated and negatively correlated with the levels of miR\u201031 in lupus T cells. Manipulation of miR\u201031 expression in lupus T cells restored the expression of IL\u20102 at both the messenger RNA and protein levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MicroRNA\u201031 is a novel enhancer of IL\u20102 production during T cell activation. Dysregulation of miR\u201031 and its target, RhoA, could be a novel molecular mechanism underlying the IL\u20102 deficiency in patients with SLE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34596","type":"journal-article","created":{"date-parts":[[2012,6,26]],"date-time":"2012-06-26T22:01:13Z","timestamp":1340748073000},"page":"3715-3725","source":"Crossref","is-referenced-by-count":96,"title":["Identification of microRNA\u201031 as a novel regulator contributing to impaired interleukin\u20102 production in T cells from patients with systemic lupus 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