# Neutralization of Microbiota-Derived Corisin Shows Early Amelioration of Advanced Pulmonary Fibrosis

## TL;DR

Blocking a microbiota-derived peptide called corisin rapidly reduces inflammation and fibrosis in advanced lung disease in mice.

## Contribution

Short-term corisin neutralization is shown to alleviate established pulmonary fibrosis in a mouse model.

## Key findings

- Anti-corisin therapy reduces inflammatory cell counts and epithelial apoptosis in fibrotic lungs.
- Corisin neutralization decreases collagen deposition and extracellular matrix accumulation.
- Treatment lowers Ashcroft fibrosis scores and lung hydroxyproline content.

## Abstract

What are the main findings?
Anti-corisin monoclonal antibody therapy rapidly improves inflammatory and fibrotic endpoints in established pulmonary fibrosis.Corisin neutralization reduces epithelial cell injury and extracellular matrix accumulation in fibrotic lungs.

Anti-corisin monoclonal antibody therapy rapidly improves inflammatory and fibrotic endpoints in established pulmonary fibrosis.

Corisin neutralization reduces epithelial cell injury and extracellular matrix accumulation in fibrotic lungs.

What are the implications of the main findings?
Corisin represents a druggable microbiota-derived mediator sustaining fibrosis beyond disease initiation.Therapeutic targeting of corisin may complement or extend current treatments for progressive fibrotic lung disease.

Corisin represents a druggable microbiota-derived mediator sustaining fibrosis beyond disease initiation.

Therapeutic targeting of corisin may complement or extend current treatments for progressive fibrotic lung disease.

Background: Corisin, a microbiota-derived proapoptotic peptide, has emerged as a key mediator of epithelial injury, inflammation, and acute exacerbation in fibrotic lung disease. Although acute corisin inhibition prevents exacerbations in experimental models, its therapeutic impact on established pulmonary fibrosis remains unclear. This study evaluated the short-term efficacy of corisin neutralization in advanced transforming growth factor-β1 (TGF-β1)-driven lung fibrosis. Methods: Male TGF-β1 transgenic mice with established fibrosis were allocated to computed tomography-matched groups and treated intraperitoneally with an anti-corisin monoclonal antibody (clone 21A) or control IgG every two days for one week. Bronchoalveolar lavage fluid (BALF) analysis, histopathology, assessment of apoptosis, Ashcroft scoring, and lung hydroxyproline quantification were performed on day 8. Results: Anti-corisin treatment significantly reduced BALF inflammatory cell counts, including macrophages and lymphocytes. Histological analyses demonstrated decreased alveolar epithelial apoptosis, reduced collagen deposition, and significantly lower Ashcroft fibrosis scores. Lung hydroxyproline content was also markedly decreased, indicating attenuation of extracellular matrix accumulation. Conclusions: Short-term neutralization of microbiota-derived corisin rapidly alleviates inflammation, epithelial injury, and fibrotic remodeling in advanced TGF-β1-induced pulmonary fibrosis. These findings identify corisin as an upstream driver of ongoing fibrogenesis and support its potential as a therapeutic target in progressive fibrotic lung disease.