Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis

ABSTRACT Background This study aims to summarize the similarities and differences in immune cell characteristics, and potential therapeutic targets between systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) and idiopathic pulmonary fibrosis (IPF). Methods This study included SSc‐ILD a...

Full description

Saved in:
Bibliographic Details
Main Authors: Shuai Shao, Siyu Cao, Yusha Chen, Zhijin Zhang, Tong Zhaohui
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:The Clinical Respiratory Journal
Subjects:
Online Access:https://doi.org/10.1111/crj.70072
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850156046705754112
author Shuai Shao
Siyu Cao
Yusha Chen
Zhijin Zhang
Tong Zhaohui
author_facet Shuai Shao
Siyu Cao
Yusha Chen
Zhijin Zhang
Tong Zhaohui
author_sort Shuai Shao
collection DOAJ
description ABSTRACT Background This study aims to summarize the similarities and differences in immune cell characteristics, and potential therapeutic targets between systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) and idiopathic pulmonary fibrosis (IPF). Methods This study included SSc‐ILD and SSc‐nonILD patients who were admitted to Beijing Chaoyang Hospital between April 4th, 2013, to June 30th, 2023. Publicly available datasets, including peripheral blood monocular cell (pbmc) single‐cell data, SSc, SSc‐ILD pbmc transcriptome data, and SSc‐ILD, IPF lung tissue transcriptome data were analyzed. Statistical analyses were conducted using the SPSS and R software, employing standard statistical methods and bioinformatics packages such as Seurat, DESeq2, enrichR, and CellChat. Results The results revealed that the CD4+/CD8+ T cell ratio of pbmc in SSc‐ILD patients was significantly higher than in SSc‐nonILD patients. In IPF patients, an elevated CD4+/CD8+ T cell ratio was also observed in progressive group, and Treg and mature CD4+ T cells might cause this change. JAK–STAT pathway and the cytokine–cytokine receptor interaction pathway were activated in peripheral blood T cells of IPF patients. The CD30, CD40, and FLT3 signaling pathways were found to play crucial roles in T cell interactions with other immune cells among IPF patients. SPA17 as a commonly upregulated gene among SSc, SSc‐ILD, and IPF pbmc and lung, with its expression correlating positively with disease severity and lung function progression. Conclusion CD4+/CD8+ T cell ratio might associate with ILD initiation and progression; Treg cells and mature CD4+ T cells play key roles of it. SPA17 might serve as a pan‐ILD marker and associated with lung function progression.
format Article
id doaj-art-b32981c6f42c44e49f87e80e882fb88a
institution OA Journals
issn 1752-6981
1752-699X
language English
publishDate 2025-04-01
publisher Wiley
record_format Article
series The Clinical Respiratory Journal
spelling doaj-art-b32981c6f42c44e49f87e80e882fb88a2025-08-20T02:24:42ZengWileyThe Clinical Respiratory Journal1752-69811752-699X2025-04-01194n/an/a10.1111/crj.70072Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary FibrosisShuai Shao0Siyu Cao1Yusha Chen2Zhijin Zhang3Tong Zhaohui4Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao‐Yang Hospital Capital Medical University Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao‐Yang Hospital Capital Medical University Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao‐Yang Hospital Capital Medical University Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao‐Yang Hospital Capital Medical University Beijing ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao‐Yang Hospital Capital Medical University Beijing ChinaABSTRACT Background This study aims to summarize the similarities and differences in immune cell characteristics, and potential therapeutic targets between systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) and idiopathic pulmonary fibrosis (IPF). Methods This study included SSc‐ILD and SSc‐nonILD patients who were admitted to Beijing Chaoyang Hospital between April 4th, 2013, to June 30th, 2023. Publicly available datasets, including peripheral blood monocular cell (pbmc) single‐cell data, SSc, SSc‐ILD pbmc transcriptome data, and SSc‐ILD, IPF lung tissue transcriptome data were analyzed. Statistical analyses were conducted using the SPSS and R software, employing standard statistical methods and bioinformatics packages such as Seurat, DESeq2, enrichR, and CellChat. Results The results revealed that the CD4+/CD8+ T cell ratio of pbmc in SSc‐ILD patients was significantly higher than in SSc‐nonILD patients. In IPF patients, an elevated CD4+/CD8+ T cell ratio was also observed in progressive group, and Treg and mature CD4+ T cells might cause this change. JAK–STAT pathway and the cytokine–cytokine receptor interaction pathway were activated in peripheral blood T cells of IPF patients. The CD30, CD40, and FLT3 signaling pathways were found to play crucial roles in T cell interactions with other immune cells among IPF patients. SPA17 as a commonly upregulated gene among SSc, SSc‐ILD, and IPF pbmc and lung, with its expression correlating positively with disease severity and lung function progression. Conclusion CD4+/CD8+ T cell ratio might associate with ILD initiation and progression; Treg cells and mature CD4+ T cells play key roles of it. SPA17 might serve as a pan‐ILD marker and associated with lung function progression.https://doi.org/10.1111/crj.70072CD4/CD8 ratiosdisease progressionIPFSPA17SSc‐ILDT cells
spellingShingle Shuai Shao
Siyu Cao
Yusha Chen
Zhijin Zhang
Tong Zhaohui
Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis
The Clinical Respiratory Journal
CD4/CD8 ratios
disease progression
IPF
SPA17
SSc‐ILD
T cells
title Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis
title_full Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis
title_fullStr Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis
title_full_unstemmed Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis
title_short Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis
title_sort immunological features and potential biomarkers of systemic sclerosis associated interstitial lung disease and idiopathic pulmonary fibrosis
topic CD4/CD8 ratios
disease progression
IPF
SPA17
SSc‐ILD
T cells
url https://doi.org/10.1111/crj.70072
work_keys_str_mv AT shuaishao immunologicalfeaturesandpotentialbiomarkersofsystemicsclerosisassociatedinterstitiallungdiseaseandidiopathicpulmonaryfibrosis
AT siyucao immunologicalfeaturesandpotentialbiomarkersofsystemicsclerosisassociatedinterstitiallungdiseaseandidiopathicpulmonaryfibrosis
AT yushachen immunologicalfeaturesandpotentialbiomarkersofsystemicsclerosisassociatedinterstitiallungdiseaseandidiopathicpulmonaryfibrosis
AT zhijinzhang immunologicalfeaturesandpotentialbiomarkersofsystemicsclerosisassociatedinterstitiallungdiseaseandidiopathicpulmonaryfibrosis
AT tongzhaohui immunologicalfeaturesandpotentialbiomarkersofsystemicsclerosisassociatedinterstitiallungdiseaseandidiopathicpulmonaryfibrosis