MicroRNAs, The Immune System and Rheumatic Disease

Esmerina Tili; Jean-Jacques Michaille; Stefan Costinean; Carlo M. Croce

Disclosures

Nat Clin Pract Rheumatol. 2008;4(10):534-541. 

In This Article

Summary and Introduction

Summary

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.

Introduction

In 1993, small noncoding RNAs were found to be involved in Caenorhabditis elegans development.[1] Since this initial discovery, numerous small, expressed RNAs -- now termed microRNAs (miRNAs) -- have been cloned and shown to negatively regulate protein translation via an antisense RNA-RNA interaction.[2,3] Study of these miRNAs flourished during the decade after their discovery, and it is now apparent that miRNAs can potentially regulate every aspect of cellular activity, from differentiation and proliferation to apoptosis, and also modulate a large range of physiological processes from developmental timing to organogenesis.[2,4,5] Mutations, deletions, and changes in the level of expression of some miRNA genes are associated with the onset and progression of certain cancers[6] as well as a wide range of diseases.[7] Indeed, genome-wide miRNA expression analyses in different tissues and tumor types, and at different stages of differentiation, have identified unique miRNA profiles specific for the type of sample studied.[8] Similar analyses of cancer-derived cell lines have shown that miRNA expression profiles are similar for cells from the same tissue of origin.[9] On the basis of these findings, miRNA expression profiles are now being exploited for the diagnosis and prognosis of human malignancies.

This Review focuses on the well-established roles of miRNAs in hematopoiesis and the immune response. We describe the molecular action of miRNAs in the simultaneous post-transcriptional regulation of multiple targets, including genes encoding transcription factors and cytokines as well as many other transcripts previously implicated in the development and function of the immune system. The potential roles of miRNA in rheumatic disease are also discussed.

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