Pathogenesis of SSc-ILD.
- 1Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Abstract
Interstitial lung disease (ILD) is the most common internal organ manifestation of systemic sclerosis (SSc) and remains the leading cause of disease-related mortality. The disease course is variable among patients, for although ILD develops in the majority of patients, only a subset progress to severe fibrotic lung disease, reflecting considerable biological heterogeneity. SSc-ILD evolves through distinct pathogenic phases, with early immune-mediated epithelial and endothelial injury giving way to autonomous fibroblast activation, extracellular matrix remodelling and self-sustaining fibrotic pathways. Insights from genetic and epigenetic studies, single-cell technologies, experimental models and, more recently, biosamples collected during clinical trials have substantially advanced our understanding of disease mechanisms and highlighted differences between early inflammatory and established fibrotic disease. This review aims to summarise the current understanding of the cellular and molecular mechanisms underlying SSc-ILD and discuss how these advances are shaping precision medicine approaches.
BibTeX
@article{clark2026pathogenesis,
title = {{Pathogenesis of SSc-ILD.}},
author = {Kristina Elizabeth Neergaard Clark},
journal = {Journal of scleroderma and related disorders},
year = {2026},
month = oct,
doi = {10.1136/jsrd-2026-000036},
url = {https://europepmc.org/article/MED/42920932},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Pathogenesis of SSc-ILD.
AU - Kristina Elizabeth Neergaard Clark
PY - 2026
DA - 2026/10/21
JO - Journal of scleroderma and related disorders
DO - 10.1136/jsrd-2026-000036
UR - https://europepmc.org/article/MED/42920932
AB - Interstitial lung disease (ILD) is the most common internal organ manifestation of systemic sclerosis (SSc) and remains the leading cause of disease-related mortality. The disease course is variable among patients, for although ILD develops in the majority of patients, only a subset progress to severe fibrotic lung disease, reflecting considerable biological heterogeneity. SSc-ILD evolves through distinct pathogenic phases, with early immune-mediated epithelial and endothelial injury giving way to autonomous fibroblast activation, extracellular matrix remodelling and self-sustaining fibrotic pathways. Insights from genetic and epigenetic studies, single-cell technologies, experimental models and, more recently, biosamples collected during clinical trials have substantially advanced our understanding of disease mechanisms and highlighted differences between early inflammatory and established fibrotic disease. This review aims to summarise the current understanding of the cellular and molecular mechanisms underlying SSc-ILD and discuss how these advances are shaping precision medicine approaches.
SN - 2397-1983
SN - 2397-1991
ER -