The fast production of effector cytokines, such as IL-2, is essential for the autocrine function in the rapid activation of naive CD4(+) T cells. Here, we show that the microRNA (miRNA) pathway plays an important role in the posttranscriptional regulation of proinflammatory cytokines in human CD4(+) T cells. miRNAs are small noncoding molecules that act as posttranscriptional regulators of gene expression by binding to the 3' untranslated region of target mRNAs. Using microarray and deep sequencing approaches, we detected an increase in the abundance of miR-9 in activated human CD4(+) T cells. To determine the impact of miR-9 on immune responses, we analyzed its effect on two putative target genes, PRDM1, which encodes for the transcription factor Blimp-1 (B lymphocyte-induced maturation protein-1), and Bcl-6 (B cell lymphoma-6 protein). Suppression of miR-9 led to increased expression of PRDM1 and Bcl-6, which subsequently resulted in diminished secretion of IL-2 and IFN-γ. Our data provide evidence that the abundance of Blimp-1, and consequently the secretion of proinflammatory cytokines, is regulated in two ways: (i) transcriptional regulation by activation of CD4(+) T cells and (ii) posttranscriptional regulation by enhanced miR-9 expression.
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.