Single-cell dissection of chronic lung allograft dysfunction reveals convergent and distinct fibrotic mechanisms.

ABSTRACT: Chronic lung allograft dysfunction (CLAD) is the leading cause of mortality after lung transplantation, yet its molecular mechanisms remain poorly understood. To elucidate the pathogenesis of CLAD, we conducted a comprehensive single-cell transcriptomic analysis of CLAD lungs, integrating our generated datasets with approximately 1.6 million cells from 15 published studies of other fibrotic lung diseases. By applying pseudo-bulk approaches to mitigate batch effects, we identified molecular signatures specific to CLAD and those shared with idiopathic pulmonary fibrosis, COVID-19, and other fibrotic conditions. Our analysis revealed CLAD-specific cellular subsets including Fibro.AT2 cells, exhausted CD8+ T cells, and superactivated macrophages while suggesting that pathogenic keratin 17-posi

SUBMITTER: Yan Y 

PROVIDER: S-EPMC12581678 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature