linc-AAM Facilitates Gene Expression Contributing to Macrophage Activation and Adaptive Immune Responses

Although various long noncoding RNAs (lncRNAs) are specifically expressed in activated macrophages, their in vivo functions and mechanisms of action are largely unexplored. Here, we identify a long intergenic noncoding RNA associated with activated macrophage (linc-AAM) and elucidate its function and mechanisms. linc-AAM is highly expressed in activated macrophages. In vitro function analysis reveals that linc-AAM facilitates macrophage activation and promotes the expression of immune response genes (IRGs). In mechanisms, linc-AAM interacts with heterogeneous nuclear ribonucleoprotein L (hnRNPL) via two CACACA motifs, resulting in its dissociation from histone H3 to activate chromatin and facilitate transcription of IRGs. Of note, linc-AAM knockout (KO) mice manifest impaired antigen-specific cellular and humoral immune responses to ovalbumin (OVA) in vivo. Altogether, the results uncover a mechanism of lncRNA in modulating hnRNPL function and confirm that linc-AAM acts as a transcription enhancer to activate macrophages and promote adaptive immunity.