Chapter 9 - MicroRNA, an Important Epigenetic Regulator of Immunity and Autoimmunity

Abstract

MicroRNAs (miRNAs), although small in size, have attracted the attention of cell biologists and clinicians alike for their ability to regulate genome expression at the posttranscriptional level. Within two decades, miRNAs have surged to the forefront as key epigenetic regulators of diverse biological systems including the immune system in both physiological processes and pathological situations. This chapter updates our recent review article (Dai R. & Ahmed S. Ansar, Translational Research 2011; 157:163–170) with current understanding of miRNA biogenesis, miRNA regulation of innate and adaptive immunity in physiological conditions, and miRNA dysregulation in pathological states with a focus on a prototypical autoimmune disease systemic lupus erythematosus (SLE). The dysregulated miRNAs in human and murine lupus have been reported to contribute to lupus pathogenesis by regulating DNA methylation, T- and B-cell development and function, and the induction of lupus-related inflammatory cytokines and chemokines. The miRNA dysregulation during lupus pathogenesis may be caused by multiple factors comprising genetic, epigenetic, hormonal, and environmental factors. Given that SLE and many other autoimmune diseases predominantly affect females, we specifically discuss the female hormone estrogen regulation of miRNA and the sexual dimorphism of miRNA expression in the SLE setting. The stable identification of unique, signature cellular, and noncellular miRNA expression profiles that correlate with the onset/severity of autoimmune disease such as SLE holds promise as novel, and much needed diagnostic biomarkers for autoimmune disease. With a comprehensive understanding of the pathogenic role of miRNA in autoimmune disease and advent of innovative techniques for effective targeting of miRNA in vivo, we anticipate the development of miRNA-based therapeutic strategies in the near future for treating SLE and other inflammatory autoimmune diseases in clinical applications.