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

  • Rujuan Dai
    Affiliations
    Center for Molecular Medicine and Infectious Diseases (CMMID), Department of Biomedical Sciences and Pathology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech/Virginia Polytechnic Institute and State University, Blacksburg, VA
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  • S. Ansar Ahmed
    Correspondence
    Reprint requests: S. Ansar Ahmed, Department of Biomedical Sciences and Pathology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, 1410 Prices Fork Road, Blacksburg, VA 24061-0342
    Affiliations
    Center for Molecular Medicine and Infectious Diseases (CMMID), Department of Biomedical Sciences and Pathology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech/Virginia Polytechnic Institute and State University, Blacksburg, VA
    Search for articles by this author
Published:February 02, 2011DOI:https://doi.org/10.1016/j.trsl.2011.01.007
      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.

      Abbreviations:

      Ago (Argonaute), AID (activation-induced cytidine deaminase), AML-1 (acute myeloid leukaemia-1), CDK-2 (cyclin-dependent kinase 2), CNS (central nervous system), DGCR8 (DiGeorge syndrome critical region protein 8), DNMT1 (DNA methyltransferase 1), EAE (experimental allergic encephalitis), ER (estrogen receptor), Foxo (forkhead transcription factor O), HRT (hormone replacement therapy), IFN (interferon), IL (interleukin), IRF-5 (IFN regulatory factor 5), IRAK-1 (interleukin-1 receptor-associated kinase 1), KLF13 (Kruppel-like factor 13), LPS (lipopolysaccharide), M-CSFR (macrophage colony-stimulating factor receptor), MCP-1 (monocyte chemoattractant protein 1), MMP (matrix metallopeptidase), MOG35–55 (myelin oligodendrocyte glycoprotein35-55), MS (multiple sclerosis), MyD88 (myeloid differentiation primary response protein 88), NF-κB (nuclear factor-κB), NFI-A (nuclear factor 1 A-type), nts (nucleotides), OA (osteoarthritis), OCP (oral contraceptive pills), PAMP (pathogen-associated molecular pattern), PBMC (peripheral blood mononuclear cell), PCR (polymerase chain reaction), pri-miRNA (primary miRNA transcripts), pre-miRNA (precursor miRNAs), PTEN (phosphatase and tensin homolog), RA (rheumatoid arthritis), RASF (synovial fibroblast), RISC (RNA-induced silencing complex), RT-PCR (reverse transcription PCR), SLE (systemic lupus erythematosus), SNP (single-nucleotide polymorphism), STAT (signal transducer and activator of transcription), TCR (T-cell receptor), Th (T helper), TLR (Toll-like receptor), TNF (tumor necrosis factor), TRAF6 (tumor necrosis factor receptor-associated factor 6), Tregs (regulatory T cells), UTR (untranslated region)
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