Mesenchymal Stem Cell-Derived Exosome-Containing Linc00632 Regulates GATA Binding Protein-3 Expression in Allergic Rhinitis by Interacting with Enhancer of Zeste Homolog 2 to Inhibit T Helper Cell 2 Differentiation.

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is regarded as one of the most common allergic disease of nasal mucosa affecting many people worldwide. Long noncoding RNAs are critical modulators affecting AR progression, whereas the pathogenesis of Linc00632 in the development of AR remains unclear. METHODS: T helper cell 2 (Th2) differentiation of CD4+ T cells was measured by flow cytometry. Real-time quantitative PCR assay and Western blot were applied to determine the levels of RNA and proteins, respectively. The interleukin (IL)-4 and IL-13 levels were quantitatively assessed through ELISA. Subcellular fractionation was conducted to detect the cellular localization of Linc00632. RNA immunoprecipitation experiment was employed to validate the interaction relationship between Linc00632 and enhancer of zeste homolog 2 (EZH2). Chromatin immunoprecipitation assay was used for determination of protein-DNA interactions. RESULTS: The expression of Linc00632 was significantly decreased by 4 times in nasal mucosa of AR patients. Human umbilical cord mesenchymal stem cell-derived exosome dramatically inhibited Th2 differentiation, decreased GATA binding protein-3 (GATA-3) protein expressions and IL-4 levels by about 2 times in CD4+ T cells. Knockdown Linc00632 partially reversed the effects of exosomes on Th2 differentiation, IL-4 and IL-13 levels, and GATA-3 expression. Linc00632 overexpression could suppress Th2 differentiation of CD4+ T cells, reduced IL-4 and IL-13 levels, and GATA-3 expressions roughly 2 times. Linc00632 repressed the expression of GATA-3 by interacting with EZH2. GATA-3 overexpression partially reversed the effect of Linc00632 on Th2 differentiation of CD4+ T cells. CONCLUSION: Linc00632 acted as a suppression factor in Th2 differentiation by inhibiting the expression of GATA-3 via interacting with EZH2, which might provide a new insight for understanding the action mechanism of Linc00632 in AR.