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MiR-29b regulates Th2 cell differentiation in asthma by targeting inducible B7-H3 and STAT3
Wenjing Gu1, Gang Li2, Weili Zhang1
1Department of Respiratory Medicine Children's Hospital of Soochow University Suzhou China.
Background:
MicroRNAs play an important role in T cell responses. However, how microRNAs regulate Th cells in asthma remains poorly defined.
Objective:
In this study, we investigated the mechanism and pathways of miR-29b regulating Th cells in asthma, in order to find new targets for asthma.
Methods:
We detected miR-29b, B7-H3 and STAT3 in the peripheral blood of children with asthma, explored the relationship between these molecules and their effects on T cells through in vitro cell culture, and verified it by animal model.
Results:
MiR-29b levels were decreased in the peripheral blood mononuclear cells from children with asthma. Vitro studies found that the expression of miR-29b in macrophages was decreased and the expression of B7-H3 and STAT3 was increased after house dust mite (HDM) stimulation. After down-regulation of miR-29b in macrophages, the expressions of B7-H3 and STAT3 in macrophages were increased and T cells differentiate into Th2 cells. After the addition of B7-H3 or STAT3 antibodies, the differentiation of naive T cells into Th2 cells was reduced. In OVA induced mice asthmatic model, after the up-regulation of miR-29b in lung, the expression of B7-H3 and STAT3 decreased in the lung tissues of mice, and the expression of Th2 cells and type II cytokine decreased simultaneously. The pathological changes of lung tissues were also alleviated.
Conclusion:
The expression of miR-29b is decreased in asthmatic children. MiR-29b can inhibit Th2 cell differentiation by inhibiting B7-H3 and STAT3 pathways at the same time, and reduce asthmatic immune inflammation.
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