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The role of miR-29c/B7-H3 axis in children with allergic asthma
Xinxing Zhang1, Xin Zhao2, Huiming Sun1
1Department of Respiratory Disease, Children's Hospital of Soochow University, Soochow University, Suzhou, China.
Background:
MicroRNAs play roles in the pathogenesis of bronchial asthma. However, the mechanism of miR-29c in allergic asthma remains unclear. This study is to elucidate the regulation of Th cell differentiation by miR-29c in mononuclear macrophages.
Methods:
A total of 52 children with asthma exacerbation and 26 children as controls were enrolled in the study. CD14+ monocytes were isolated from the peripheral blood. Differential expressions of microRNAs were evaluated using microarray analysis and miR-29c expression in monocytes was determined by qRT-PCR. The plasma B7-H3 was determined by ELISA. Transfection studies and luciferase reporter assay were performed to confirm target gene of miR-29c and its function.
Results:
Compared to controls, 88 miRNAs in blood monocytes were up-regulated and 41 miRNAs down-regulated including miR-29c in asthma children. Children with asthma exacerbation had significantly lower level of miR-29c and higher level of plasma B7-H3 compared to controls (both P < 0.05). Functional studies based on luciferase reporter assay and immunofluorescence staining suggest that B7-H3 is the direct target of miR-29c and transfection anti-miR-29c into macrophages could enhance ROR-γt and GATA-3 expression in co-cultured CD4+ T cells and increase levels of IL-4 and IL-17 in supernatants.
Conclusion:
The axis of miR-29c/B7-H3 plays an important role in children with asthma through regulating Th2/Th17 cell differentiation and may provide new targets for treatment of asthma.
Insights
MicroRNA-29c (miR-29c) is reduced in children with asthma exacerbation. Lower miR-29c and higher B7-H3 levels are linked to asthma, suggesting a new therapeutic target for allergic asthma.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- MicroRNAs are implicated in bronchial asthma pathogenesis.
- The specific role of miR-29c in allergic asthma remains largely unknown.
- Understanding miR-29c's regulation of T-helper cell differentiation in macrophages is crucial.
Purpose of the Study:
- To elucidate the regulatory role of miR-29c in T-helper cell differentiation within mononuclear macrophages.
- To investigate the miR-29c/B7-H3 axis in pediatric asthma.
Main Methods:
- Isolated CD14+ monocytes from children with asthma exacerbation and controls.
- Utilized microarray analysis, qRT-PCR, and ELISA to assess miRNA and protein expression.
- Performed transfection studies and luciferase reporter assays to confirm miR-29c targets and function.
Main Results:
- Asthma patients exhibited significantly lower miR-29c and higher plasma B7-H3 levels compared to controls.
- B7-H3 was identified as a direct target of miR-29c.
- Inhibition of miR-29c enhanced Th2/Th17 cell differentiation markers (ROR-γt, GATA-3) and cytokine production (IL-4, IL-17).
Conclusions:
- The miR-29c/B7-H3 axis plays a significant role in pediatric asthma.
- This axis regulates Th2 and Th17 cell differentiation.
- The miR-29c/B7-H3 pathway presents potential therapeutic targets for asthma treatment.
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