The fibrosis puzzle of systemic sclerosis-associated ILD and the quest for targeted interventions

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality in systemic sclerosis, marked by complex immunopathogenic mechanisms and progressive fibrosis. Recent advances have illuminated key cellular players as T cells, macrophages, dendritic cell...

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Main Authors: Bohdana Doskaliuk, Liubomyr Zaiats, Nazar Sahan, Yuliya Fedorchenko, Olga Antymys, Roman Yatsyshyn
Format: Article
Language:English
Published: SAGE Publishing 2025-08-01
Series:Therapeutic Advances in Respiratory Disease
Online Access:https://doi.org/10.1177/17534666251366023
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author Bohdana Doskaliuk
Liubomyr Zaiats
Nazar Sahan
Yuliya Fedorchenko
Olga Antymys
Roman Yatsyshyn
author_facet Bohdana Doskaliuk
Liubomyr Zaiats
Nazar Sahan
Yuliya Fedorchenko
Olga Antymys
Roman Yatsyshyn
author_sort Bohdana Doskaliuk
collection DOAJ
description Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality in systemic sclerosis, marked by complex immunopathogenic mechanisms and progressive fibrosis. Recent advances have illuminated key cellular players as T cells, macrophages, dendritic cells, and profibrotic mediators such as TGF-β, PDGF, and CTGF, alongside emerging roles for epigenetic reprogramming in sustaining fibroblast activation. This narrative review synthesizes current understanding of immune-fibrotic crosstalk and critically evaluates both established therapies (e.g., mycophenolate mofetil, nintedanib, tocilizumab, and rituximab) and novel targeted approaches. Particular attention is given to emerging immunomodulatory, antifibrotic, and cell-based therapies, including CAR-T and mesenchymal stem cell treatments, as well as the potential of epigenetic modulators repurposed from oncology. By bridging basic science and clinical practice, this review outlines the evolving therapeutic landscape of SSc-ILD and highlights opportunities for future research and personalized intervention.
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series Therapeutic Advances in Respiratory Disease
spelling doaj-art-54053f103cf64f228b4af416c58fdbfd2025-08-20T03:46:34ZengSAGE PublishingTherapeutic Advances in Respiratory Disease1753-46662025-08-011910.1177/17534666251366023The fibrosis puzzle of systemic sclerosis-associated ILD and the quest for targeted interventionsBohdana DoskaliukLiubomyr ZaiatsNazar SahanYuliya FedorchenkoOlga AntymysRoman YatsyshynSystemic sclerosis-associated interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality in systemic sclerosis, marked by complex immunopathogenic mechanisms and progressive fibrosis. Recent advances have illuminated key cellular players as T cells, macrophages, dendritic cells, and profibrotic mediators such as TGF-β, PDGF, and CTGF, alongside emerging roles for epigenetic reprogramming in sustaining fibroblast activation. This narrative review synthesizes current understanding of immune-fibrotic crosstalk and critically evaluates both established therapies (e.g., mycophenolate mofetil, nintedanib, tocilizumab, and rituximab) and novel targeted approaches. Particular attention is given to emerging immunomodulatory, antifibrotic, and cell-based therapies, including CAR-T and mesenchymal stem cell treatments, as well as the potential of epigenetic modulators repurposed from oncology. By bridging basic science and clinical practice, this review outlines the evolving therapeutic landscape of SSc-ILD and highlights opportunities for future research and personalized intervention.https://doi.org/10.1177/17534666251366023
spellingShingle Bohdana Doskaliuk
Liubomyr Zaiats
Nazar Sahan
Yuliya Fedorchenko
Olga Antymys
Roman Yatsyshyn
The fibrosis puzzle of systemic sclerosis-associated ILD and the quest for targeted interventions
Therapeutic Advances in Respiratory Disease
title The fibrosis puzzle of systemic sclerosis-associated ILD and the quest for targeted interventions
title_full The fibrosis puzzle of systemic sclerosis-associated ILD and the quest for targeted interventions
title_fullStr The fibrosis puzzle of systemic sclerosis-associated ILD and the quest for targeted interventions
title_full_unstemmed The fibrosis puzzle of systemic sclerosis-associated ILD and the quest for targeted interventions
title_short The fibrosis puzzle of systemic sclerosis-associated ILD and the quest for targeted interventions
title_sort fibrosis puzzle of systemic sclerosis associated ild and the quest for targeted interventions
url https://doi.org/10.1177/17534666251366023
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