MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases

MicroRNAs (miRNAs) are newly discovered, small, noncoding ribonucleic acids (RNAs) that play critical roles in the regulation of host genome expression at the posttranscriptional level. During last 20 years, miRNAs have emerged as key regulators of various biological processes including immune cell lineage commitment, differentiation, maturation, and maintenance of immune homeostasis and normal function. Thus, it is not surprising that dysregulated miRNA expression patterns now have been documented in a broad range of diseases including cancer as well as inflammatory and autoimmune diseases. This rapidly emerging field has revolutionized our understanding of normal immunoregulation and breakdown of self-tolerance. This review focuses on the current understanding of miRNA biogenesis, the role of miRNAs in the regulation of innate and adaptive immunity, and the association of miRNAs with autoimmune diseases. We have discussed miRNA dysregulation and the potential role of miRNAs in systemic lupus erythematosus (SLE), rheumatoid arthritis, and multiple sclerosis. Given that most autoimmune diseases are female-predominant, we also have discussed sex hormone regulation of miRNAs in inflammatory responses, with an emphasis on estrogen, which now has been shown to regulate miRNAs in the immune system. The field of miRNA regulation of mammalian genes has tremendous potential. The identification of specific miRNA expression patterns in autoimmune diseases as well as a comprehensive understanding of the role of miRNA in disease pathogenesis offers promise of not only novel molecular diagnostic markers but also new gene therapy strategies for treating SLE and other inflammatory autoimmune diseases. (Translational Research 2011;157:163-179)