Banner image placeholder
Banner image

Epithelial cell-derived lumican modulates extracellular matrix dynamics in early-life airways disease.


Journal article


F. Puttur, W. Traves, M. G. Martin, Samuele Di Carmine, F. Fercoq, D. C. Gaboriau, Lewis J Entwistle, Laura Yates, R. Joulia, Sara Patti, Helen Stoelting, Ciara Campbell, Mindy L Gore, S. Walker, Lola E Loewenthal, P. Molyneaux, Leo M. Carlin, S. Saglani, Clare M Lloyd
Journal of Allergy and Clinical Immunology, 2025

Semantic Scholar DOI PubMed
Cite

Cite

APA   Click to copy
Puttur, F., Traves, W., Martin, M. G., Carmine, S. D., Fercoq, F., Gaboriau, D. C., … Lloyd, C. M. (2025). Epithelial cell-derived lumican modulates extracellular matrix dynamics in early-life airways disease. Journal of Allergy and Clinical Immunology.


Chicago/Turabian   Click to copy
Puttur, F., W. Traves, M. G. Martin, Samuele Di Carmine, F. Fercoq, D. C. Gaboriau, Lewis J Entwistle, et al. “Epithelial Cell-Derived Lumican Modulates Extracellular Matrix Dynamics in Early-Life Airways Disease.” Journal of Allergy and Clinical Immunology (2025).


MLA   Click to copy
Puttur, F., et al. “Epithelial Cell-Derived Lumican Modulates Extracellular Matrix Dynamics in Early-Life Airways Disease.” Journal of Allergy and Clinical Immunology, 2025.


BibTeX   Click to copy

@article{f2025a,
  title = {Epithelial cell-derived lumican modulates extracellular matrix dynamics in early-life airways disease.},
  year = {2025},
  journal = {Journal of Allergy and Clinical Immunology},
  author = {Puttur, F. and Traves, W. and Martin, M. G. and Carmine, Samuele Di and Fercoq, F. and Gaboriau, D. C. and Entwistle, Lewis J and Yates, Laura and Joulia, R. and Patti, Sara and Stoelting, Helen and Campbell, Ciara and Gore, Mindy L and Walker, S. and Loewenthal, Lola E and Molyneaux, P. and Carlin, Leo M. and Saglani, S. and Lloyd, Clare M}
}

Abstract

BACKGROUND Airway remodelling is a prominent pathological feature in pre-school wheeze (PSW) and school-age asthma (SA). Although the relationships between altered lung function, extracellular matrix (ECM) changes and airway remodelling are described in PSW and SA, the underlying mechanisms remain undefined.

OBJECTIVES To investigate mechanisms resulting in altered airway ECM-landscape in PSW (1-5 years) and SA (6-16 years) and track ECM-dynamics in house dust mite (HDM) exposed neonatal mice.

METHODS We applied spatial transcriptomics, confocal and second harmonic generation microscopy, in PSW and SA endobronchial biopsies and in HDM-exposed neonatal mice lungs to reveal transcriptional, phenotypic and structural ECM-associated changes during allergic airway inflammation.

RESULTS Spatial transcriptomic analysis of the airways of children with PSW and SA revealed increased gene expression for fibrillar collagens-I, -II, -III, and basement membrane collagen-VI in fibroblast rich regions in both diseases. Similarly, increased collagen-III and collagen-VI deposition with exaggerated collagen fibril disorganisation were observed in the peribronchial regions of HDM-exposed neonatal mice. Collagen disorganisation was also evident in the airways of children with PSW and SA and was accompanied by increased production of bronchial epithelial cell derived lumican and increased airway lumican in PSW, SA, and HDM-exposed neonatal mice. Lumican directly altered primary healthy airway fibroblast function, increasing proliferation and collagen production.

CONCLUSIONS We demonstrate a previously uncharacterised role of collagen-associated phenotypic and geometric changes in early-life airway remodelling and show lumican as a crucial remodelling factor associated with collagen organisation in PSW and SA.



Translate to