Background: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is an endotype of chronic rhinosinusitis with nasal polyps characterized by more severe symptoms, a stronger association with asthma and a greater recurrence risk. It is unknown whether DNA hydroxymethylation could influence ECRSwNP. Methods: Hydroxymethylated DNA immunoprecipitation sequencing was carried out in three distinct groups (control, ECRSwNP and NECRSwNP). Additional qRT-PCR, immunohistochemistry and analysis of the receiver operating characteristic curve were performed. Results: Between ECRSwNP and NECRSwNP, 26 genes exhibited differential DNA hydroxymethylation. Consistent with their hydroxymethylation level, GNAL, INPP4A and IRF4 expression levels were significantly different between ECRSwNP and the other two groups. The receiver operating characteristic curve revealed that INPP4A mRNA has a high predictive accuracy for ECRSwNP. Conclusion: DNA hydroxymethylation regulates the expression of multiple genes in ECRSwNP. INPP4A mRNA was markedly decreased in ECRSwNP polyps and can predict ECRSwNP.
Purpose Previous studies have shown the role of ten-eleven translocation 2 (TET2) in CD4 + T cells. However, its function in CD4 + T cells under allergic inflammation is unclear. We aimed to investigate the epigenomic distribution of DNA 5-hydroxymethylcytosine (5hmC) and the role of TET2 in CD4 + T cells of allergic rhinitis (AR). Methods The hMeDIP-seq was performed to identify sequences with 5hmC deposition in CD4 + T cells of AR patients. Tet2- deficient or wild type mice were stimulated with ovalbumin (OVA) to develop an AR mouse model. The histopathology in nasal mucosae, Th1/Th2/Treg/Th17 cell percentage, concentrations of Th-related cytokines, expression of Tet and differential hydroxymethylated genes (DhMG), and the global deposition of 5hmC in sorted CD4 + T cells were detected. Results Epigenome-wide 5hmC landscape and DhMG in the CD4 + T cells of AR patients were identified. Tet2 depletion did not led to spontaneous inflammation. However, under the stimulation of allergen, OVA, loss of Tet2 resulted in the exacerbation of allergic inflammation, which was characterized by severer allergic symptoms, more inflammatory cells infiltrating the nasal lamina propria, sharper imbalances between Th1/Th2 and Treg/Th17 cells, and excessive secretion of OVA-specific IgE and Th2-related cytokines. Moreover, altered mRNA production of several DhMG and sharp decrease in 5hmC deposition were also observed in Tet2 -deficient OVA-exposed mice. Conclusions TET2 may regulate DNA 5hmC, DhMG expressions, and CD4 + T cell balance in AR.
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