Long non‐coding RNA MALAT1 promotes Th2 differentiation by regulating microRNA‐135b‐5p/GATA‐3 axis in children with allergic rhinitis

Abstract

Abstract Allergic rhinitis (AR) threatens patient survival. CD4+ T cells play key roles in AR progression. Long non‐coding RNAs (lncRNAs) are key regulators of cell differentiation. Therefore, we investigated the molecular mechanism of the lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) in AR. Expression levels of MALAT1, microRNA (miR)‐135b‐5p, interleukin‐4 (IL‐4), and GATA‐binding protein 3 (GATA‐3) in the nasal mucosa of AR patients were quantified. CD4+ T cells were isolated from the peripheral blood of healthy volunteers and treated with ovalbumin (OVA) and Th2 inducers. After MALAT1 and miR‐135b‐5p levels changed in CD4+ T cells, the proportion of IL‐4‐expressing cells and the levels of IL‐4 and GATA‐3 in OVA‐induced CD4+ T cells were determined. Binding relationships among MALAT1, miR‐135b‐5p, and GATA‐3 were predicted and verified. Rescue experiments were performed to confirm the role of the MALAT1/miR‐135b‐5p/GATA‐3 axis in Th2 differentiation of CD4+ T cells. MALAT1, IL‐4, and GATA‐3 expression was upregulated, whereas miR‐135b‐5p expression was downregulated, in patients with AR. MALAT1 knockdown or miR‐135b‐5p overexpression in CD4+ T cells notably decreased the proportion of IL‐4‐expressing cells and downregulated GATA‐3 and IL‐4 expression in OVA‐induced CD4+ T cells. MALAT1 and GATA‐3 exhibited competitive binding toward miR‐135b‐5p. MALAT1 facilitated CD4+ T cell Th2 differentiation via the miR‐135b‐5p/GATA‐3 axis. MALAT1 facilitated AR development by facilitating CD4+ T cell Th2 differentiation via the miR‐135b‐5p/GATA‐3 axis. This study may provide guidance for clinical treatment of AR.

Keywords

• allergic rhinitis
• GATA binding protein 3
• long non‐coding RNA MALAT1
• microRNA‐135b‐5p
• T‐helper 2 differentiation