The epithelium as a barrier in lung fibrosis and cardiovascular disease

Intro

Fibrosis often begins with epithelial damage which, after prolonged injury, extends into the interstitial ECM and activates fibroblasts. This session will address how to establish the right balance between the epithelial basement membrane and fibroblasts in the interstitial ECM to improve patient outcomes.

Immune driven fibrosis in heart failure. 

Stephane Heymans, Professor of Cardiomyopathies, Head of the Centre for Heart Failure Research, Department of Cardiology, Maastricht University.

Abstract: Cardiac fibrosis is a central driver of heart failure and arrhythmias, yet the mechanisms linking inflammation to fibrotic remodeling remain incompletely understood. Recent work highlights a dynamic cardio-immune axis in which immune activation shapes fibroblast behavior and extracellular matrix remodeling. Through integrated clinical cohorts, multi-omics analyses, and experimental models, we explore how immune signals regulate fibroblast to myocyte communication and promote fibrotic remodeling in cardiomyopathies and myocarditis. Particular attention is given to the role of immune-derived glycoproteins and cellular interactions in driving pathogenic fibrosis. Understanding these mechanisms may reveal novel therapeutic opportunities to target immune-mediated cardiac remodeling and prevent progression to heart failure.

Scar Trek: when basal cells get beyond the barrier.

Gisli Jenkins, NIHR Research Professor, Margaret Turner Warwick Chair of Thoracic Medicine, Head of the Margaret Turner Warwick Centre for Fibrosing Lung Disease at the National Heart and Lung Institute, Imperial College London.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease characterised by excessive extracellular matrix deposition within the lung. Recent advances in single-cell RNA sequencing have identified distinct fibrotic populations of cells, yet their origins and spatial relationships remain incompletely understood. Spatial multi’omic profiling of human lung cells identifies the in-situ localisation of previously described IPF-enriched populations. It is known that there is a reduction in AT2 cells in IPF, which is exaggerated in patients with telomere related disorders, and there is an expansion of both basal cells and aberrant basaloid cells. We have recently identified a previously unrecognized KRT5low /KRT17⁺ epithelial population derived from airway barrier derived basal cells that progressively acquire molecular features of aberrant basaloid cells, forming a unique fibrotic niche enriched with the Secreted Phosphoprotein 1 (SPP1) positive macrophages. In addition, distinct immune–stromal niches enriched in lymphocytes and alveolar fibroblasts are also found. Functional studies demonstrated that epithelial detachment, cyclical mechanical stretch and a high TGFbeta environment drive KRT5 reduction, providing a novel mechanism for the emergence of this transitional state. Furthermore, basal cells migrate on a fibronectin matrix which is increased in fibrotic Interstitial Lung Diseases. These findings reveal distinct fibrotic epithelial niches in IPF and support a model in which alveolar epithelial loss induces aberrant basaloid differentiation and fibroblast activation, with subsequent airway traction and epithelial detachment generating a secondary niche enriched in basal-derived KRT5low 95 /KRT17 cells and SPP1⁺ macrophages.Abstract: TBD