T-cell Multiomic Analysis Identifies Subsets and Mechanisms of Interaction with Epithelial Cells in Idiopathic Pulmonary Fibrosis Article Swipe
Júlia Miranda Ribeiro Bazzano
,
L Silva
,
Erin M. Wilfong
,
Ciara M. Shaver
,
Lorraine B. Ware
,
Nicholas E. Banovich
,
Jonathan A. Kropski
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.11.19.689037
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.11.19.689037
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scarring and respiratory failure, with a median survival of 3–5 years. While T-cell numbers are elevated in IPF lungs, their contributions to fibrosis beyond inflammation remain poorly understood. Here, we performed multiplex imaging and single-cell RNA and protein profiling on ∼90,000 CD3⁺ T-cells from control and fibrotic lungs, revealing eleven distinct subsets of CD4⁺ and CD8⁺ T-cells. Among these, we identified a rare CD56⁺ regulatory T-cell subset that is highly activated in fibrosis and exhibits a sustained immunosuppressive phenotype. CXCR4/MIF signaling emerged as a central axis mediating T-cell–epithelial interactions, while epidermal growth factor receptor (EGFR) and TGFβ pathways dominated in multiple T-cell subsets. Our findings demonstrate that T-cells in IPF adopt nonclassical activation patterns, driven by epithelial interactions and the fibrotic microenvironment. These studies provide a foundation for exploring novel therapeutic strategies in IPF lungs by modulating T-cell behavior and communication networks.
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- Type
- article
- Landing Page
- https://doi.org/10.1101/2025.11.19.689037
- https://www.biorxiv.org/content/biorxiv/early/2025/11/19/2025.11.19.689037.full.pdf
- OA Status
- green
- References
- 58
- OpenAlex ID
- https://openalex.org/W4416366215
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https://openalex.org/W4416366215Canonical identifier for this work in OpenAlex
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https://doi.org/10.1101/2025.11.19.689037Digital Object Identifier
- Title
-
T-cell Multiomic Analysis Identifies Subsets and Mechanisms of Interaction with Epithelial Cells in Idiopathic Pulmonary FibrosisWork title
- Type
-
articleOpenAlex work type
- Publication year
-
2025Year of publication
- Publication date
-
2025-11-19Full publication date if available
- Authors
-
Júlia Miranda Ribeiro Bazzano, L Silva, Erin M. Wilfong, Ciara M. Shaver, Lorraine B. Ware, Nicholas E. Banovich, Jonathan A. KropskiList of authors in order
- Landing page
-
https://doi.org/10.1101/2025.11.19.689037Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2025/11/19/2025.11.19.689037.full.pdfDirect link to full text PDF
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-
YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
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-
https://www.biorxiv.org/content/biorxiv/early/2025/11/19/2025.11.19.689037.full.pdfDirect OA link when available
- Cited by
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0Total citation count in OpenAlex
- References (count)
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58Number of works referenced by this work
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