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Monday, July 8, 2013

MicroRNAs – the hot new thing in allergic inflammation regulation

While investigations of microRNAs [miRNA] and their role in transcription in disease have been growing for the last decade, more recently they have come under the scrutiny of immunologists searching for signs of miRNA dysregulation in allergic inflammation.  This month, Lu and Rothenberg review the evidence to-date and give us some very interesting news on miRNA in several atopic diseases [J Allergy Clin Immunol 2013; 132(1): 3-13].

Lu and Rothenberg start with a review of the general pathophysiology of miRNAs, which effect gene transcription networks by silencing posttranscriptional gene expression of mRNA.  One miRNA can modulate multiple genes and one gene may be targeted by many miRNAs.  miRNAs are also known to modify DNA methylation and histone acetylation, as well as interact with transcription factors.  The authors comment that miRNAs have been found in exosomes in cell-free body fluids, raising the intriguing possibility of their usefulness as peripheral biomarkers.  

The authors present the current knowledge of miRNA profiles that have been identified in allergic asthma, eosinophilic esophagitis, atopic dermatitis, and allergic rhinitis.  By far the most abundant information is available for allergic asthma.  One particular miRNA – miR-21 – has been well characterized in experimental models of asthma.  Lu and Rothenberg discuss findings that point to miR-21 involvement in TH1-TH2 polarization.  In these models, miR-21 is over-expressed in experimental asthma and strongly suppresses expression of IL-12p35 mRNA, permitting TH2 bias in the immune response.  They note that studies of MiR-21 deficiency in asthma mice report increases in IL-12p35 and IFN-g production and concomitant decreases in eosinophilia and IL-4 in bronchoaveolar fluid.  Lu and Rothenberg discuss other miRNAs that have been identified in allergic inflammatory processes such as miR-126 and the Let miRNA family. Critical miRNAs associated with airway smooth muscle function are also discussed along with the early results of miRNA profiling in human asthma. 

Important findings on critical miRNAs identified in eosinophilic esophagitis are reviewed.  The authors discuss miR-21 mechanisms in eosinophilic esophagitis that are consistent with those reported for allergic asthma.  One miRNA, miR-146a, has been characterized in eosinophilic esophagitis as a repressor of TH1 responses through dysregulation of Treg suppression in a STAT1 dependent manner. Peripherally circulating miR-146a and miR-223 in patients with eosinophilic esophagitis are discussed as promising non-invasive biomarkers for diagnosis and therapy response. 

Lu and Rothenberg further review miRNA profiles that have been characterized in atopic dermatitis and allergic rhinitis, noting that miRNA data in AR is currently sparse.  Also discussed is the role of miRNA in eosinophil development in light of the collaborative interaction between miR-21 and miR-223 in eosinophil viability, proliferation, and maturation. 

The authors provide an excellent table that summarizes miRNAs common to allergic asthma, eosinophilic esophagitis, and atopic dermatitis.  Concluding, Lu and Rothenberg offer a number of topics for future research focus.  

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