Watson, Carolin K, Schloesser, Daniela, Fundel-Clemens, Katrin, Lerner, Carmen, Gabler, Svenja, Baskaran, Praveen, Wohnhaas, Christian T, Dichtl, Stefanie, Huber, Heinrich J, Ask, Kjetil, Gantner, Florian, Viollet, Coralie, Thomas, Matthew J, Ramirez, Fidel, Murray, Peter J and El Kasmi, Karim C (2023) Antifibrotic Drug Nintedanib Inhibits CSF1R to Promote IL-4-associated Tissue Repair Macrophages. American journal of respiratory cell and molecular biology, 68 (4). pp. 366-380. ISSN 1535-4989

Abstract

Profibrotic and prohomeostatic macrophage phenotypes remain ill-defined, both and , impeding the successful development of drugs that reprogram macrophages as an attractive therapeutic approach to manage fibrotic disease. The goal of this study was to reveal profibrotic and prohomeostatic macrophage phenotypes that could guide the design of new therapeutic approaches targeting macrophages to treat fibrotic disease. This study used nintedanib, a broad kinase inhibitor approved for idiopathic pulmonary fibrosis, to dissect lung macrophage phenotypes during fibrosis-linked inflammation by combining and bulk and single-cell RNA-sequencing approaches. In the bleomycin model, nintedanib drove the expression of IL-4/IL-13-associated genes important for tissue regeneration and repair at early and late time points in lung macrophages. These findings were replicated in mouse primary bone marrow-derived macrophages exposed to IL-4/IL-13 and nintedanib. In addition, nintedanib promoted the expression of IL-4/IL-13 pa

Item Type:	Article
Date Deposited:	28 Dec 2024 00:45
Last Modified:	28 Dec 2024 00:45
URI:	https://oak.novartis.com/id/eprint/56191