Spatial Transcriptomics Reveals Coordinated Endothelial and Epithelial Activator Protein-1 Activation in Chronic Lung Allograft Dysfunction

Authors

• Yasufumi Goda
• Tatsuhiko Naito
• Mudassir M Banday
• Andrew S Potter
• Igor Odintsov
• Kapil Patel
• Nicole Davis
• Stefi Lee
• Amit Gaggar
• Ivan Rosas
• Gabriel Loor
• Don Hayes
• Nirmal S Sharma

Language

English

Publication Date

6-1-2026

Journal

The Journal of Heart and Lung Transplantation

DOI

10.1016/j.healun.2026.01.028

PMID

41663041

PMCID

PMC13274917

PubMedCentral® Posted Date

6-18-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Chronic lung allograft dysfunction (CLAD) limits long-term lung graft survival, yet its specific gene expression profiles remain unclear. We performed comprehensive spatial transcriptomic analyses of human lungs from CLAD patients, non-CLAD transplant recipients, and non-transplanted controls. In CLAD, AP-1 target genes, including JUNB and FOS, were significantly upregulated in both the epithelium and endothelium, whereas anti-fibrotic genes such as A2M and surfactant proteins (SFTPA1,2) were upregulated in non-CLAD. The lymphocyte population in CLAD was predominantly composed of T cells, with elevated JAK3-IL7R signaling. TNF and IL-17 signaling pathways were commonly activated in both the epithelium and endothelium, with JUNB and FOS serving as central hubs within pro-inflammatory, pro-fibrotic gene networks. These findings suggest that coordinated AP-1 activation and shared inflammatory and fibrotic signaling across epithelial and endothelial compartments may drive CLAD. Our results highlight the transcriptionally active roles of both compartments and provide new mechanistic insights into CLAD pathogenesis.

Keywords

Humans, Lung Transplantation, Transcription Factor AP-1, Spatial Transcriptomics, Male, Allografts, Primary Graft Dysfunction, Female, Chronic Disease, Middle Aged, Transcriptome, Signal Transduction, Gene Expression Profiling, Graft Rejection, Lung transplantation, Chronic lung allograft dysfunction, Spatial transcriptomics, Activator protein-1, Fibrogenesis, IL-17

Published Open-Access

yes

Recommended Citation

Goda, Yasufumi; Naito, Tatsuhiko; Banday, Mudassir M; et al., "Spatial Transcriptomics Reveals Coordinated Endothelial and Epithelial Activator Protein-1 Activation in Chronic Lung Allograft Dysfunction" (2026). Faculty, Staff and Students Publications. 6784.
https://digitalcommons.library.tmc.edu/baylor_docs/6784