# Temporal Dynamics of Pulmonary Fibrosis and Immune Dysregulation in a Collagen V-Driven Systemic Sclerosis Model

## TL;DR

This study explores how collagen V triggers lung fibrosis and immune issues in a mouse model resembling systemic sclerosis, offering insights into early disease mechanisms.

## Contribution

The study introduces a novel murine model (IMU-COLV) that captures early fibrotic and immune changes linked to collagen V in systemic sclerosis.

## Key findings

- Lung remodeling in the IMU-COLV model begins with immune infiltration and progresses to airway-centered fibrosis.
- COLV immunization leads to endothelial activation and altered collagen architecture, resembling features of SSc-related lung disease.
- The model mirrors histological patterns seen in idiopathic pulmonary fibrosis and chronic lung allograft dysfunction.

## Abstract

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by progressive fibrosis and immune dysregulation, with lung involvement being a major cause of morbidity and mortality. Type V collagen (COLV), a cryptic self-antigen, has been implicated in the pathogenesis of fibrosis in both SSc and lung allograft dysfunction. To characterize the early histological, molecular, and immunological events associated with lung remodeling following immunization with COLV in a murine model (IMU-COLV), and to establish a temporal framework for fibrosis progression. Using a time-course design, lung tissue from IMU-COLV mice was analyzed at multiple intervals post-immunization. Histopathological assessment, immunohistochemistry, and gene expression analysis were performed to evaluate inflammation, endothelial activation, extracellular matrix remodeling, and collagen composition. We observed a progressive and spatially organized pattern of lung remodeling, beginning with peribronchovascular immune infiltration and culminating in airway-centered fibrosis. These changes were accompanied by dynamic endothelial activation, increased expression of profibrotic markers, and alterations in collagen architecture particularly involving COLV. The remodeling pattern closely mirrors histological features observed in early SSc-associated interstitial lung disease and other fibrotic conditions, such as idiopathic pulmonary fibrosis and chronic lung allograft dysfunsion. The IMU-COLV model recapitulates key early features of SSc-related lung fibrosis, highlighting COLV’s potential role as a driver of immune-mediated tissue remodeling. These findings provide a valuable platform for investigating the mechanisms underlying fibrogenesis and for testing targeted interventions in the early phases of pulmonary fibrosis.