ABSTRACTIncreasing evidence has uncovered the essential roles of long noncoding RNAs (lncRNAs) in biological and pathological functions of dendritic cells (DCs) among patients with systemic lupus erythematosus (SLE). However, whether lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) could modulate DCs, especially in the inflammation of SLE, remains largely unknown. Fifteen SLE patients and fifteen age-matched healthy controls were included, and their monocyte-derived dendritic cells (moDCs) were cultured in vitro. Our research identified that the expression ofNEAT1was significantly increased in moDCs of SLE patients and positively correlated with disease activity. Interleukin 6 (IL-6) from both plasma and secreted supernatants of moDCs was also elevated in the SLE group. In addition, regulation ofNEAT1in moDCs by transfection could lead to the corresponding change in IL-6 generation. While formiR-365a-3p, a micro-RNA that can bind with the 3’ UTR region ofIL6andNEAT1, it may serve as a negative modulator since its overexpression could result in the reduction of IL-6 levels and vice versa. Additionally, the elevation inNEAT1expression could increase the secretion of IL-6 by specifically binding tomiR-365a-3p, reducing the negative modulatory effects ofmiR-365a-3pon theIL6target gene, which suggested that elevatedNEAT1expression could function as the competing endogenous RNA (ceRNA). In conclusion, our findings indicate thatNEAT1can efficiently spongemiR-365a-3pto upregulate expression and secretion of IL-6 in moDCs, suggesting that theNEAT1/miR-365a-3p/IL6axis may be involved in the development of SLE disease.