Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 150, Issue 6, Pages 1460-1475Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2022.05.030
Keywords
Chronic rhinosinusitis with nasal polyps; glucagon-like peptide-1 receptor; microRNA-21-5p; type 2 inflammation
Categories
Funding
- National Natural Science Foundation of China [81800882, 81870698, 82171109]
- National Key R&D Pro-gram of China [2018YFC0116800]
- program for the Changjiang scholars and innovative research team [IRT13082]
- Beijing municipal administration of hospitals Mission/Dengfeng plan [SML20150203, DFL20190202]
- Beijing municipal administration of hospitals clinical medicine development of special funding support [XMLX201816]
- public welfare development and reform pilot project [2019-10]
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This study found that miR-21-5p is upregulated in the nasal mucosa of patients with CRSwNP and is positively correlated with indicators of type 2 inflammation. In a mouse model, miR-21 knockout attenuated type 2 inflammation and downregulated genes associated with type 2 inflammation. miR-21-5p aggravates type 2 inflammation in the nasal mucosa of patients with CRSwNP by targeting the glucagon-like peptide-1 receptor/IL-33 signaling pathway.
Background: It has been known that chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammation-dominated disease; however, the reasons causing such type of mucosal inflammation in CRSwNP are not well elucidated. Objective: We sought to investigate the role of microRNA-21-5p (miR-21-5p) in regulating mucosal type 2 inflammation in CRSwNP. Methods: miR-21-5p expression was detected in nasal mucosa of patients with CRSwNP. Correlations between miR-21-5p and indicators of type 2 inflammation were further analyzed. miR-21 knockout mice were used to explore the role of miR-21-5p in a murine model of eosinophilic (E) CRSwNP. Target gene of miR-21-5p related to type 2 inflammation in CRSwNP was identified. Results: The upregulated miR-21-5p in the nasal mucosa of patients with CRSwNP, compared with control subjects, was expressed higher in patients with ECRSwNP than in patients with nonECRSwNP. miR-21-5p expression was positively correlated with mucosal eosinophil infiltrations and the expression of type 2 inflammatory cytokines. In the CRSwNP mice, miR-21 knockout significantly attenuated type 2 inflammation, as indicated by eosinophil infiltrations and expression of cytokines/chemokines in nasal mucosa and lavage fluid; moreover, genes associated with type 2 inflammation were extensively downregulated at the transcriptome level in miR-21 knockout mice. Glucagon-like peptide-1 receptor, which was negatively correlated with miR-21-5p expression in human nasal mucosa, was identified as the target of miR-21-5p. Overexpression of miR-21-5p induced IL-33 expression, whereas glucagon-like peptide-1 receptor agonist decreased IL-33 production in airway epithelial cells. Conclusions: miR-21-5p aggravates type 2 inflammation in the nasal mucosa of patients with CRSwNP via targeting glucagon-like peptide-1 receptor/IL-33 signaling, which may be a potential therapeutic target for CRSwNP.
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