Non-coding RNA LINC01010 regulates macrophage polarization and innate immune functions by modulating NFκB signaling pathway

Innate immune response is regulated by tissue resident or infiltrating immune cells such as macrophages (M phi) that play critical role in tissue development, homeostasis, and repair of damaged tissue. However, the epigenetic mechanisms that regulate M phi plasticity and innate immune functions are not well understood. Long non-coding RNA (lncRNA) are among the most abundant class of transcriptome but their function in myeloid cell biology is less explored. In this study, we deciphered the regulatory role of previously uncharacterized lncRNAs in M phi polarization and innate immune responses. Two lncRNAs showed notable changes in their levels during M1 and M2 M phi differentiation. Our findings indicate that LINC01010 expression increased and AC007032 expression decreased significantly. LINC01010 exhibit myeloid cell-specificity, while AC007032.1 is ubiquitous and expressed in both myeloid and lymphoid (T cells, B cells and NK cells) cells. Expression of these lncRNAs is dysregulated in periodontal disease (PD), a microbial biofilm-induced immune disease, and responsive to lipopolysaccharide (LPS) from different oral and non-oral bacteria. Knockdown of LINC01010 but not AC007032.1 reduced the surface expression of M phi differentiation markers CD206 and CD68, and M1M phi polarization markers MHCII and CD32. Furthermore, LINC01010 RNAi attenuated bacterial phagocytosis, antigen processing and cytokine secretion suggesting its key function in innate immunity. Mechanistically, LINC01010 knockdown M phi treated with Escherichia coli LPS exhibit significantly reduced expression of multiple nuclear factor kappa B pathway genes. Together, our data highlight functional role of a PD-associated lncRNA LINC01010 in shaping macrophage differentiation, polarization, and innate immune activation. Long non-coding RNA LINC01010 expression is increased during M1 and M2 polarized monocyte-derived macrophage differentiation and exhibits impaired expression in inflamed gingiva. Knockdown of LINC01010 downregulated M1M phi phenotype markers and attenuated bacterial phagocytosis, antigen processing and cytokine secretion. LINC01010 RNAi impaired NF kappa B signaling in M phi treated with E. coli LPS suggesting its key function in innate immunity. image