TY - JOUR T1 - RANKL contributes to lung tissue repair via promoting type II epithelial cell proliferation JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.5029 VL - 56 IS - suppl 64 SP - 5029 AU - Habibie Habibie AU - Shanshan Song AU - Kurnia Putri AU - Carian Boorsma AU - Robbert Cool AU - Xinhui Wu AU - Reinoud Gosens AU - Yizhou Wang AU - Wim Quax AU - Peter Olinga AU - Corry-Anke Brandsma AU - Wim Timens AU - Janette Burgess AU - Barbro Melgert Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/5029.abstract N2 - Higher levels of receptor activator for NF-κβ ligand (RANKL) are found in serum of emphysema patients. RANKL is a well-known stimulator of bone tissue degradation, possibly explaining the association of COPD with osteoporosis. However, RANKL is also reported to be involved in epithelial cell regeneration in breast and thymus. Given RANKL is produced directly in lung tissue, we hypothesized a role for RANKL in lung epithelial cell regeneration. The aim of this study was to elucidate the role of RANKL in lung epithelial repair.Mouse soluble RANKL (sRANKL) treatment of murine precision-cut lung slices resulted in a higher number of proliferating cells compared to untreated controls. We also found that sRANKL stimulated proliferation of type II alveolar (A549 cells) but not airway (16HBE) epithelial cells. Using an organoid model of epithelial development by co-culturing primary EpCAM+ cells with fibroblasts, we found higher numbers of alveolar organoids in cultures derived from murine epithelial cells upon sRANKL treatment compared to control. Importantly, this effect was similar in RANKL-treated organoids derived from epithelial cells isolated from lung tissue of COPD patients. The effect of sRANKL was abrogated upon addition of osteoprotegerin, the soluble, inhibitory, receptor for RANKL.In conclusion, we found that sRANKL promotes type II alveolar epithelial cell proliferation and may therefore contribute to lung tissue repair. Our data suggest that the higher levels of RANKL found in emphysema, may reflect an attempt at epithelial repair by the lung to counteract the lung tissue destruction that characterizes emphysema.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 5029.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.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 -