# PDGFRα+ fibroblast ablation exacerbates pathologic features in a model of house dust mite-induced allergenic asthma

## TL;DR

Removing PDGFRα+ fibroblasts in mice worsens asthma symptoms by increasing inflammation and immune cell activation.

## Contribution

This study reveals that PDGFRα+ fibroblasts are crucial for immune balance in asthma.

## Key findings

- Ablation of PDGFRα+ fibroblasts reduces lipofibroblasts and alters extracellular matrix gene expression.
- Loss of PDGFRα+ fibroblasts increases mucous production and proinflammatory immune cells in asthma.
- PDGFRα+ fibroblast ablation leads to dysregulated airway immune composition and remodeling.

## Abstract

Asthma, a chronic inflammatory airway disease, remains a major global health concern. Fibroblasts, the cell type responsible for tissue repair and fibrosis, are therefore a potential therapeutic target for asthma-related lung disease. However, the role of fibroblasts in the onset and progression of asthma is poorly understood. Thus, we sought to determine the effects of fibroblast loss on lung homeostasis and asthma development using a transgenic mouse model to ablate PDGFRα+ fibroblasts. We observed a consistent reduction in PDGFRα+ cells (75-85% in the mesenchyme), which persisted for several months. The PDGFRα+ fibroblast-ablated lungs exhibited a reduced number of lipofibroblasts, altered extracellular matrix gene expression and increased neutrophils in both the bronchoalveolar lavage fluid and the lung tissues under steady-state conditions. When asthma was induced, we found that loss of PDGFRα+ fibroblasts resulted in increased mucous production, neutrophil activation and proinflammatory cells, such as interstitial macrophages and eosinophils, which can worsen asthma. These findings highlight the essential roles of PDGFRα+ fibroblasts in maintaining immune balance and how their loss leads to dysregulated airway immune composition and remodeling, contributing to asthma pathogenesis.

Summary: This study demonstrates that PDGFRα+ fibroblast ablation worsens asthma pathology by elevating neutrophil numbers and activation, highlighting fibroblast–immune crosstalk in asthma pathogenesis.