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- W4229366975 abstract "Lungs of patients with Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by severe alveolar tissue destruction and impaired repair responses. Our preliminary data from the Melgert lab has shown that Receptor Agonist of NFkB signalling Ligand (RANKL) can induce alveolar differentiation of lung organoids and proliferation of type II epithelial cells in murine lungs, implicating this osteokine in lung tissue repair. Moreover, the inflammatory cytokine IL1β, which is found in higher levels in the lungs of patients with COPD, has been described to induce RANKL production in stromal cells in the bone. We therefore hypothesized that lung tissue destruction in COPD induces IL1β and subsequent RANKL production as a repair mechanism. However, it is currently unclear whether IL1β also induces local RANKL production in the lung and whether this is altered in COPD. To test this, we first explored a publicly available single-cell sequencing dataset comprising IL1β-treated murine lung organoids and found that RANKL mRNA expression was strongly induced in fibroblasts treated with IL1β. To further explore the effects of IL1β, primary lung fibroblasts from patients with or without COPD were treated with IL1β for 72 hours. IL1β strongly induced production of RANKL protein in control fibroblasts and notably this effect was not observed in COPD-derived fibroblasts. IL1b strongly induced production of RANKL protein in control fibroblasts and notably this effect was not observed in COPD-derived fibroblasts. Combined, these results suggest that IL1b-driven RANKL production by lung fibroblasts may be involved in alveolar repair and this mechanism may be defective in COPD." @default.
- W4229366975 created "2022-05-10" @default.
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- W4229366975 date "2022-03-10" @default.
- W4229366975 modified "2023-09-23" @default.
- W4229366975 title "IL1ß induces RANKL secretion in control but not COPD lung fibroblasts" @default.
- W4229366975 doi "https://doi.org/10.1183/23120541.lsc-2022.18" @default.
- W4229366975 hasPublicationYear "2022" @default.
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