Significance statement

Inflammasome activation and autophagy are fundamental eukaryotic pathways that have multiple effects on a series of diseases including cancer, diabetes, atherosclerosis, and neurodegenerative diseases. Our work elucidates the link between lincRNA-Cox2 and the inflammasome-autophagy crosstalk in macrophage and microglia, revealing a role for lncRNAs in activation of NLRP3 inflammasome and autophagy. As a representative of neuroinflammation-dependent diseases, multiple sclerosis (MS) is believed to be caused by Th17 cells and microglia-mediated central nervous system (CNS) inflammation and demyelination. Experimental autoimmune encephalomyelitis (EAE) serves as an ideal animal model for MS. Here, we demonstrate that lincRNA-Cox2 knockdown results in protection from EAE, and exhibits notable increased resting microglia (CD11b⁺CD45^med), inhibited the IL-1β secretion and enhanced autophagy in CNS, which might provide new insights into the original mechanism and new opportunities for therapeutic intervention in neuroinflammation-dependent diseases.