TY - JOUR T1 - Epigenetic regulation via PRMT7 controls monocyte migration and COPD pathogenesis JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.OA2949 VL - 58 IS - suppl 65 SP - OA2949 AU - Thomas Conlon AU - Gizem Gunes AU - Aicha Jeridi AU - Rin Kim AU - Gerald Burgstaller AU - Stijn Verleden AU - Tobias Stöger AU - Gunnar Dittmar AU - Melanie Königshoff AU - Oliver Eickelberg AU - Henrik Watz AU - Robert Schneider AU - Ali Önder Yildirim Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/OA2949.abstract N2 - COPD is an inflammatory lung disease characterized by progressive airflow limitation and tissue destruction. Cigarette smoke (CS) is a major risk factor for the development of the disease but only 15% of smokers develop disease which suggests a potential role for epigenetic regulation in disease pathogenesis. Histone methylation by protein arginine methyltransferases (PRMTs) is one of the most important epigenetic controls and implicated in immune system dysfunction and inflammation. Here we investigate the role of arginine methylation as an important determinant of monocyte-driven inflammatory responses in COPD.PRMT7 expression is increased in COPD patients (1.3 fold with P<0.01) compared to non-diseased smokers and localized mainly in macrophages. Using CS-induced animal models of COPD, we observed that mice with reduced expression of Prmt7 demonstrated impaired recruitment of macrophages to the lungs by 40% compared to WT animals following CS-exposure which prevented emphysema development (airspace enlargement 22µm vs 26µm, P<0.01) and improved diffusion capacity (56% vs 61%). Moreover, this impaired recruitment in macrophages protected against alveolar epithelial cell death. Mechanistically, we discovered that PRMT7 induced methylation of histones, in particular, H3R2me1 and H3R2me2, at enhancers regulating Rap1a expression, which is crucial for MAPK signaling, integrin activation, and the subsequent adhesion and migration ability of monocytes.In summary, we demonstrate that PRMT7 is upregulated in COPD patients compared to non-diseased smokers and regulates histone epigenetic marks controlling recruitment of monocyte-derived macrophages to the lungs and subsequent COPD immunopathogenesis.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA2949.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -