miR-29b Reverses T helper 1 cells/T helper 2 cells Imbalance and Alleviates Airway Eosinophils Recruitment in OVA-Induced Murine Asthma by Targeting Inducible Co-Stimulator

Abstract

Asthma is a complex chronic disease and the pathogenesis is still not entirely clear. In this study, we aimed to clarify the role and mechanism of miR-29b in the development of asthma. We observed that miR-29b levels were decreased in the lung and spleen of OVA-induced asthmatic mice. Reverse transcription-quantitative polymerase chain reaction and flow cytometry demonstrated that the inducible co-stimulator (ICOS) expression at mRNA and protein levels was elevated in the lung of asthmatic mice, and miR-29b expression in the lung of asthmatic mice was negatively associated with ICOS mRNA levels by Pearson Correlation analysis. Additional, flow cytometry showed that the percentage of CD4<sup>+</sup>ICOS<sup>+</sup> T cells in the lung and spleen was regulated by miR-29b, and dual luciferase reporter assay confirmed ICOS was a target gene of miR-29b. Furthermore, miR-29b overexpression in asthmatic mice was induced with miR-29b agomir by intranasal administration; miR-29b alleviated total inflammatory cell infiltration and CCL24 levels, decreased IL-5 levels in bronchoalveolar lavage fluid and serum, and upregulated IFN-γ expression in serum. This study demonstrates that miR-29b targets ICOS, thereby reverses the imbalance of T helper 1 cells (Th1)/Th2 responses and decreases eosinophils recruitment in the airway, which are key features of allergic airway inflammation. Therefore, miR-29b might be an attractive candidate target for asthma treatment.

MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease

“…One of these miRNAs is miR-29b, which is involved in the development of asthma. This miRNA indirectly affects to Th2 response by regulating T-box transcription factors and IFN-γ production in T helper cells ( 181 ), so a lower expression of this miRNA in asthmatic lung allows a higher production of IFN-γ in order to recover Th1/Th2 balance in asthmatic lungs ( 182 ). According to miR-19a, Simpson et al.…”

Streptococcus pneumoniae aminopeptidase N regulates dendritic cells that attenuates type‐2 airway inflammation in murine allergic asthma

“…The experimental groups were designed as follows:‐ sham induction by the sterile PBS control group, asthma model group with OVA (Sigma‐Aldrich, St. Louis, MO, USA) induction and asthma model with PepN treatment group. For OVA‐induced allergic asthma, mice were intraperitoneally sensitized with 100 μg OVA suspended in 1 mg of aluminium hydroxide (Thermo Scientific, Waltham, MA, USA) in 200 μl of sterile PBS on days 0 and 7, followed by eight aerosol challenges with 5% (w/v) OVA in PBS for 30 min per day from day 14 to 21 (Yan et al, 2019). The control group mice were treated in the same way with PBS at the same time points.…”

Differentially expressed circular RNAs in a murine asthma model

“…in the present study, four differentially expressed circrnas were validated by qPCR, of which two were significantly upregulated and two were significantly downregulated. The regulatory network of circrna and mirna indicated that two of these upregulated circrnas (circ_0000455 and circ_0000629) could target mir-29b and mir-15a, respectively, which were previously reported to be negatively correlated with the occurrence of allergic reactions (41,42). The expression levels of inducible co-stimulator, a target gene of mir-29b, were also previously shown to be elevated in the lungs of asthmatic mice, and promoted Th2 cytokine production and eosinophilic inflammation (43).…”