Long non-coding RNA nuclear paraspeckle assembly transcript 1 promotes activation of T helper 2 cells via inhibiting...

T helper (Th) 2 cell-medicated immune response participates in various immune diseases, including systemic lupus erythematosus (SLE). Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to be associated with T helper 2 (Th2) cell activation. Here, we demonstrated the molecular mechanism of NEAT1 in regulating Th2 cell activation. We found that NEAT1 was located in nucleus. NEAT1 overexpression promoted the levels of Th2-related cytokines IL-4, IL-5 and IL-13 in CD4⁺ T cells. Moreover, NEAT1 up-regulation reduced Th1-related cytokine INF-γ production and enhanced the levels of Th17-related cytokines IL-17 in CD4⁺ T cells. STAT6 deficiency reduced the levels of IL-4, IL-5, IL-13 and IL-17 enhanced the levels of INF-γ in CD4⁺ T cells, which was rescued by NEAT1 overexpression. Moreover, NEAT1 promoted STAT6 protein expression, whereas NEAT1 had no effect on the expression of STAT6 mRNA. Furthermore, NEAT1 interacted with STAT6, inhibited the ubiquitination of STAT6 in CD4⁺ T cells. In conclusion, our work has confirmed that NEAT1 promotes STAT6 expression by inhibiting STAT6 ubiquitination, thereby promoting Th2 cell activation. Thus, our work may highlight novel insights into the molecular mechanism of NEAT1 in regulating Th2 cell activation.