Abstract
MicroRNAs (miRNAs) are ~22 nucleotide single-stranded RNAs that regulate the stability of target messenger RNAs (mRNAs) via selective binding to specific sites at the 3'-UTR. This triggers repression in translation and mRNA degradation. It has been estimated that ~60% of all mRNAs are under the control of miRNAs. Among the known hundreds of miRNAs, some are considered master regulators controlling either a single or multiple cellular pathways. Some miRNAs are known to affect development and cell differentiation, while others are implicated in immunity and autoimmune diseases. A very interesting example is miR-146a, which has been reported to be downregulated in systemic lupus erythematosus and upregulated in rheumatoid arthritis. This miRNA plays a dominant role in the regulation of the innate immune responses. The overexpression or underexpression of miRNAs can influence specific targets and pathways, leading to autoimmune disease phenotypes, and this is also supported by some in vivo studies. Targeting miRNAs could represent a valid future therapeutic option for autoimmune diseases. This discussion will focus on the current understanding in the function of miR-146a in endotoxin tolerance and cross-tolerance, and how it may contribute to modulate the overproduction of known pathogenic cytokines.
Highlights
Antinuclear antibodies can be detected in up to 25% of the population; only 5 to 7% are afflicted with an autoimmune disease
We have previously shown that B6 mice with an introgressed homozygous NZB chromosome 1 (c1) interval (70 to 100 cM) develop high titers of antinuclear antibodies and severe glomerulonephritis
Using subcongenic mice with shorter c1 intervals, we found that expansion of TH1, TH17, and TFH cells was closely associated with the severity of glomerulonephritis
Summary
Hyperactivity of the type I interferon (IFN) pathway is involved in the pathogenesis of systemic lupus erythematosus (SLE). ILT3 expression levels on PDCs and MDCs from 18 patients and 10 controls were studied by flow cytometry. Results: The rs11540761 SNP in the extracellular region was associated with decreased cell surface expression of ILT3 on circulating MDCs and to a lesser extent PDCs in SLE patients. The cytoplasmically located rs1048801 SNP was not associated with a change in DC expression of ILT3. Both SNPs were significantly and independently associated with increased levels of serum type I IFN activity in SLE patients. A64 Nonlymphoma hematological malignancies in systemic lupus erythematosus M Lu1*, R Ramsey-Goldman, S Bernatsky, M Petri, S Manzi, MB Urowitz, D Gladman, PR Fortin, E Ginzler, E Yelin, S-C Bae, DJ Wallace, S Jacobsen, MA Dooley, CA Peschken, GS Alarcón, O Nived, L Gottesman, L Criswell, G Sturfelt, L Dreyer, JL Lee, AE Clarke1 1Division of Clinical Epidemiology, McGill University Health Centre, Montreal, QC, Canada; 2Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 3Johns Hopkins University School of Medicine, Baltimore, MD, USA; 4West Penn Allegheny Health System, Pittsburgh, PA, USA; 5Toronto Western Hospital, Toronto, ON, Canada; 6Division of Rheumatology, Université de Laval, QC, Canada; 7State University of New York - Downstate Medical Center, Brooklyn, NY, USA; 8Division of Rheumatology, University of California San Francisco, San Francisco, CA, USA; 9The Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea; 10Cedars-Sinai Medical Center/David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 11Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 12University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 13University of Manitoba, Winnipeg, MB, Canada; 14The University of Alabama, Birmingham, AL, USA; 15Lund University Hospital, Lund, Sweden; 16Rigshospitalet and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark Arthritis Research & Therapy 2012, 14(Suppl 3):A64
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