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Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease [Duke]

ABSTRACT: Interstitial lung disease (ILD) is present in over 60% of patients with systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. Profibrotic monocyte-derived alveolar macrophages (MoAM) play a causal role in the pathogenesis of pulmonary fibrosis in animal models where their persistence in the niche requires signaling through the Colony Stimulating Factor 1 Receptor (CSF1R). We hypothesized that the presence and proportion of MoAM in bronchoalveolar lavage (BAL) fluid from patients with SSc-ILD may be a biomarker of ILD severity. To test this hypothesis, we performed BAL in 9 prospectively enrolled patients with SSc-ILD on imaging and 13 healthy controls and analyzed the cellular fraction using flow cytometry and single-cell RNA sequencing. Compared to healthy controls, patients with SSc-ILD showed increased abundance of MoAM and interstitial macrophages in BAL fluid that was associated with worse lung function and lung disease on imaging. We identified changes in the MoAM transcriptome as a function of treatment with mycophenolate, an effective therapy for SSc-ILD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303858 | GEO | 2025/07/31

REPOSITORIES: GEO

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Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease [Northwestern]

Project description:Interstitial lung disease (ILD) is present in over 60% of patients with systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. Profibrotic monocyte-derived alveolar macrophages (MoAM) play a causal role in the pathogenesis of pulmonary fibrosis in animal models where their persistence in the niche requires signaling through the Colony Stimulating Factor 1 Receptor (CSF1R). We hypothesized that the presence and proportion of MoAM in bronchoalveolar lavage (BAL) fluid from patients with SSc-ILD may be a biomarker of ILD severity. To test this hypothesis, we performed BAL in 9 prospectively enrolled patients with SSc-ILD on imaging and 13 healthy controls and analyzed the cellular fraction using flow cytometry and single-cell RNA sequencing. Compared to healthy controls, patients with SSc-ILD showed increased abundance of MoAM and interstitial macrophages in BAL fluid that was associated with worse lung function and lung disease on imaging. We identified changes in the MoAM transcriptome as a function of treatment with mycophenolate, an effective therapy for SSc-ILD.

2025-07-31 | GSE303859 | GEO

Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease

Project description:Interstitial lung disease (ILD) is present in over 60% of patients with systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. Profibrotic monocyte-derived alveolar macrophages (MoAM) play a causal role in the pathogenesis of pulmonary fibrosis in animal models where their persistence in the niche requires signaling through the Colony Stimulating Factor 1 Receptor (CSF1R). We hypothesized that the presence and proportion of MoAM in bronchoalveolar lavage (BAL) fluid from patients with SSc-ILD may be a biomarker of ILD severity. We performed spatial transcriptomics to localize profibrotic MoAM to the alveolar space and identified expansion of interstitial macrophages spilling into the alveolar space. Our findings suggest that the proportion of profibrotic MoAM and interstitial macrophages in BAL fluid may serve as a biomarker of SSc-ILD and credential them as possible targets for therapy.

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Novel Pulmonary Imaging Biomarkers and Cutaneous Gene Expression Subsetting for Patient Selection and Outcome Assessment in the Dasatinib Treatment of Systemic Sclerosis-associated Interstitial Lung Disease

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Expression of mRNA from lung tissue from Systemic Sclerosis patients with interstitial lung disease (SSc-ILD) and healthy controls (HC)

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2016-08-01 | E-GEOD-81292 | biostudies-arrayexpress

Expression of miRNA from lung tissue from Systemic Sclerosis patients with interstitial lung disease (SSc-ILD) and healthy controls.

2016-08-01 | E-GEOD-81293 | biostudies-arrayexpress

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2021-03-30 | GSE156310 | GEO

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