Global Profiling of Differentiating Macrophages Identifies Novel Functional Long Non-coding RNAs Regulating Polarization and Innate Immune Responses

Macrophages (M{varphi}) are functionally dynamic immune cells that bridge innate and adaptive immune responses. However, the underlying epigenetic mechanisms that control the macrophage plasticity and innate immune functions are not well-elucidated. Here we performed transcriptome profiling of differentiating M1M{varphi} and M2M{varphi} and identified thousands of previously known and novel lncRNAs. We characterized three M{varphi}-enriched lncRNAs (LRRC75A-As1, GAPLINC and AL139099.5) with novel functions in M{varphi} differentiation, polarization and innate immunity. Knockdown of LRRC75A-As1, and GAPLINC downregulated M{varphi} differentiation markers CDw93 and CD68, and skewed macrophage polarization by decreasing M1 markers but had no significant impact on M2 markers. LRRC75A-As1, and GAPLINC RNAi in M{varphi} attenuated bacterial phagocytosis, antigen processing and inflammatory cytokine secretion supporting their functional role in potentiating innate immune functions. Mechanistically, lncRNA knockdown perturbed the expression of multiple cytoskeleton signaling thereby impairing M{varphi} migration suggesting their critical role in regulating macrophage polarity and motility. Together, our results show that M{varphi} acquire a unique repertoire of lncRNAs to shape differentiation, polarization and innate immune functions.