miR-143-3p Inhibits the Differentiation of Th1 Cells in Rhinosinusitis by Regulating TET1/IFN-γ Signaling.
Dysregulated microRNAs (miRNAs) are a hallmark of chronic rhinosinusitis, especially chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to investigate the role of miR-143-3p in chronic rhinosinusitis. miR-143-3p and mRNA levels were calculated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expressed was determined by Western blot. The infiltration of CD4 cells and eosinophils was analyzed using immunohistochemistry and hematoxylin and eosin staining. The binding sites between miR-143-3p and TET1 were predicted with TargetScan and verified using luciferase assay. The DNA methylation of interferon-gamma (IFN-γ) was predicted using DNA methylation-specific RT-qPCR assay. The interaction between TET1 and IFN-γ was confirmed using the chromatin immunoprecipitation assay. CD4+ T cell polarization was analyzed using flow cytometry. miR-143-3p was downregulated in CRSwNP patients, mediating nasal polyp presence. Overexpressed miR-143-3p promoted the differentiation of T helper 1 (Th1) cells. miR-143-3p targeted and downregulated the expression of TET1, which was upregulated in CRSwNP patients. TET1-mediated DNA methylation of IFN-γ, inducing its downregulation. Overexpressed TET1 inhibited Th1 differentiation and promoted the Th1 cell to Th2 polarization. miR-143-3p promotes the differentiation of anti-inflammatory Th1 cells in CRSwNP via regulating TET1/IFN-γ axis.