The CCL20–integrin α5β1 interaction enhances TGF-β/Smad signaling to promote fibroblast activation in pulmonary fibrosis

Suosi Liu, Qianrong Wang, Jiali Min, Ziying Zhang, Yu Zhang, Jiahui Yang, Yuexin Tan, Lupin Tan, Min Yin, Yan Zhang, Xiangning Tang, Hong Peng, Zhenkun Xia, Yang Xiao, Zhiguang Zhou, Xia Li () and Shanshan Liu ()
Additional contact information
Suosi Liu: The Second Xiangya Hospital of Central South University
Qianrong Wang: The Second Xiangya Hospital of Central South University
Jiali Min: The Second Xiangya Hospital of Central South University
Ziying Zhang: The Second Xiangya Hospital of Central South University
Yu Zhang: The Second Xiangya Hospital of Central South University
Jiahui Yang: The Second Xiangya Hospital of Central South University
Yuexin Tan: The Second Xiangya Hospital of Central South University
Lupin Tan: The Second Xiangya Hospital of Central South University
Min Yin: The Second Xiangya Hospital of Central South University
Yan Zhang: The Second Xiangya Hospital of Central South University
Xiangning Tang: The Second Xiangya Hospital of Central South University
Hong Peng: The Second Xiangya Hospital of Central South University
Zhenkun Xia: The Second Xiangya Hospital of Central South University
Yang Xiao: The Second Xiangya Hospital of Central South University
Zhiguang Zhou: The Second Xiangya Hospital of Central South University
Xia Li: The Second Xiangya Hospital of Central South University
Shanshan Liu: The Second Xiangya Hospital of Central South University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Limited therapeutic options are available for pulmonary fibrosis because its molecular pathogenesis remains unclear. Here, we find that chemokine CCL20 expression is increased in both murine models and patients with pulmonary fibrosis. Type 2 alveolar epithelial cells are identified as the major producers of CCL20, and increased CCL20 expression results from decreased expression of the transcription factor JUN. AEC2-specific deletion of CCL20 protects mice from bleomycin-induced pulmonary fibrosis. Mechanistic studies reveal that CCL20 interacts with integrin α5β1, but not the classical receptor CCR6, on fibroblasts and subsequently enhances TGF-β/Smad signaling, which promotes the differentiation of lung fibroblasts into myofibroblasts. Antibody blockade of CCL20 or disruption of the CCL20–integrin α5β1 interaction attenuates established pulmonary fibrosis. Overall, our study highlights the CCL20–integrin α5β1–TGF-β signaling cascade as a potential therapeutic target for pulmonary fibrosis.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-64211-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64211-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-64211-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().