Exosomal long non-coding RNA GAS5 suppresses Th1 differentiation and promotes Th2 differentiation via downregulating EZH2 and T-bet in allergic rhinitis

Abstract

The imbalance of helper T cell (Th) 1/Th2 differentiation is involved in the development of allergic rhinitis (AR). Recent studies reveal the regulatory function of exosomes on Th1/Th2 differentiation. However, the key mediator in exosomes that modulate such response remains unclear. In this study, the expression of long-noncoding RNA GAS5 (LncGAS5) was detected in exosomes which were isolated from AR patient nasal mucus (AR-EXO) and ovalbumin (OVA)-stimulated nasal epithelial cells (OVA-EXO). Th1/Th2 differentiation was induced in naïve CD4+ T cells, and the percentage of IFN-γ expressing cells (Th1 cells) and IL-4 expressing cells (Th2 cells) was detected using flow cytometry. The result showed that LncGAS5 was upregulated in AR epithelial samples, AR-EXO, and OVA-EXO. The coincubation of AR-EXO and CD4+ T cells suppressed Th1 differentiation and promoted Th2 differentiation, which is mediated by LncGAS5 in AR-EXO. The LncGAS5 in AR-EXO inhibited transcription and expression of EZH2, and it also inhibited T-bet expression at mRNA and protein levels. The gain-of-function and loss-of-function experiments suggested that LncGAS5 mediates Th1/Th2 differentiation partly through downregulating T-bet and EZH2. In summary, our findings demonstrated that LncGAS5 in AR epithelium-derived exosomes is the key mediator in Th1/Th2 differentiation, providing a possible therapeutic target of AR.