An endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis (original) (raw)

Eosinophil microRNAs Play a Regulatory Role in Allergic Diseases Included in the Atopic March

International Journal of Molecular Sciences

(1) Background: The atopic march is defined by the increased prevalence of allergic diseases after atopic dermatitis onset. In fact, atopic dermatitis is believed to play an important role in allergen sensitization via the damaged skin barrier, leading to allergic diseases such as allergic asthma and allergic rhinitis. The eosinophil, a pro-inflammatory cell that contributes to epithelial damage, is one of the various cells recruited in the inflammatory reactions characterizing these diseases. Few studies were conducted on the transcriptome of this cell type and even less on their specific microRNA (miRNA) profile, which could modulate pathogenesis of allergic diseases and clinical manifestations post-transcriptionally. Actually, their implication in allergic diseases is not fully understood, but they are believed to play a role in inflammation-related patterns and epithelial cell proliferation. (2) Methods: Next-generation sequencing was performed on RNA samples from eosinophils of individuals with atopic dermatitis, atopy, allergic rhinitis and asthma to obtain differential counts of primary miRNA (pri-miRNA); these were also analyzed for asthma-related phenotypes such as forced expiratory volume in one second (FEV 1), immunoglobulin E (IgE) and provocative concentration of methacholine inducing a 20% fall in forced expiratory volume in 1 s (PC 20) levels, as well as FEV 1 to forced vital capacity (FEV 1 /FVC) ratio. (3) Results: Eighteen miRNAs from eosinophils were identified to be significantly different between affected individuals and unaffected ones. Based on counts from these miRNAs, individuals were then clustered into groups using Ward's method on Euclidian distances. Groups were found to be explained by asthma diagnosis, familial history of respiratory diseases and allergic rhinitis as well as neutrophil counts. (4) Conclusions: The 18 differential miRNA counts for the studying phenotypes allow a better understanding of the epigenetic mechanisms underlying the development of the allergic diseases included in the atopic march.

Asthma diagnosis using integrated analysis of eosinophil microRNAs

Allergy, 2018

Asthma is a syndrome characterized by airway inflammation and obstruction. Due to its heterogeneity, the difficulties in asthma diagnosis and treatment make the discovery of new biomarkers a focus of research. So, we determined the differential miRNA expression of eosinophils between healthy and asthmatic patients and to establish a differentially expressed miRNA profile detectable in sera for use as biomarker. MicroRNAs from peripheral eosinophils from healthy and asthmatic subjects were isolated and analyzed by next generation sequencing and confirmed by quantitative PCR in 29 asthmatics and 10 healthy individuals. The levels of serum miRNAs were performed by quantitative PCR in 138 asthmatics and 39 healthy subjects. Regression analysis and Random forest models were performed. We found a set of miRNAs whose expression differs between eosinophils from asthmatics and healthy subjects. These miRNAs can classify asthmatics into two clusters that differed in the number of eosinophils ...

Pathogenic Roles of MicroRNA in the Development of Asthma

Asthma and Lung Biology [Working Title]

Asthma is a common and chronic inflammatory disease. Pathogenic mechanism underlying asthma is complicated. The inflammatory reactions in asthma have been recognized to involve mast cells, eosinophils, lymphocytes (T cells, B cells), macrophages, and dendritic cells. MicroRNA (miRNA, miR) is a group of small noncoding RNAs with 21-25 nucleotides (nt) in length, which impact biologic responses through the regulation of mRNA transcription and/or translation. MicroRNAs are related to developmental processes of many immunologic diseases. Most studies showed that regulation of miRNAs to their targeting genes appears to play an important role in the development of asthma. This chapter has discussed altered expression of miRNAs in cells and tissues from patients with asthma, in order to better understand the mechanics of pathogenesis of asthma. In addition, the regulation of miRNAs as a novel therapeutic approach will require a deeper understanding of their function and mechanism of action.

Spotlight on microRNAs in allergy and asthma

2020

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Regulating the Regulators: microRNA and Asthma

World Allergy Organization Journal, 2011

One obstacle to developing an effective therapeutic strategy to treat or prevent asthma is that the fundamental causes of asthma are not totally understood. Asthma is thought to be a chronic T H 2 immune-mediated inflammatory disease. Epigenetic changes are recognized to play a role in the initiation and maintenance of a T H 2 response. MicroRNAs (miRNAs) are key epigenetic regulators of gene expression, and their expression is highly regulated, therefore, deregulation of miRNAs may play an important role in the pathogenesis of asthma. Profiling circulating miRNA might provide the highest specificity and sensitivity to diagnose asthma; similarly, correcting potential defects in the miRNA regulation network may lead to new therapeutic modalities to treat this disease.