Findings demonstrate BET inhibition improves lung function and reduces fibrosis in bronchiolitis obliterans, highlighting macrophage polarization as a therapeutic target.
Key Points
The study aims to evaluate the role of BET inhibition in managing fibrosis associated with bronchiolitis obliterans in cGVHD.
Used a BOS model with T cell depleted bone marrow in cGVHD mice
Administered BET inhibitor (OPN-51107) and assessed lung function
Performed spectral flow cytometry, immunofluorescence, and scRNA-seq to analyze immune responses
BET inhibition improved pulmonary function tests and decreased collagen deposition in treated mice
Reduced levels of circulating pathogenic IgG1/IgM and activated T helper cells
Altered macrophage polarization, reducing profibrotic pathways in interstitial macrophages