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RESEARCH PRODUCT

MicroRNAs, the immune system and rheumatic disease.

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MicroRNAs (miRNAs) have been implicated in the pathogenesis of rheumatic disease and are, therefore, a potential target for drug development. This Review describes the well-established roles of miRNAs in hematopoiesis and the immune response, the molecular action of miRNAs in the simultaneous post-transcriptional regulation of multiple targets, and the evidence for roles of specific miRNAs in rheumatic disease. MicroRNAs (miRNAs) are short noncoding RNA molecules that modulate the expression of multiple target genes at the post-transcriptional level and are implicated in a wide array of cellular and developmental processes. In hematopoietic cells, miRNA levels are dynamically regulated during lineage differentiation and also during the course of the immune response. Mouse models have provided good evidence for miRNAs being key players in the establishment of hematopoietic lineages. Furthermore, miRNA-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response to a wide range of pathogens, spontaneously emerging tumors, and autoimmune cells. Deregulation of hematopoietic-specific miRNA expression results in defects in both central and peripheral tolerance, hematopoietic malignancies, and sometimes both. Abnormal expression of miRNAs—which is implicated in inflammation—has also been found in patients with rheumatoid arthritis. These findings identify miRNAs as critical targets for immunomodulatory drug development.