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

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

PROVIDER: PRJNA1297778 | ENA |

REPOSITORIES: ENA

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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.

2025-07-23 | GSE303048 | GEO

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

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 | GSE303858 | GEO

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

| PRJNA1293414 | ENA

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

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

| PRJNA1297777 | ENA

Epigenetic regulation of profibrotic macrophages in systemic sclerosis- associated interstitial lung disease

Project description:Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the leading cause of death in patients with systemic sclerosis (SSc) with unclear pathogenesis and limited treatment options. Evidence strongly supports an important role for profibrotic, SPP1-expressing macrophages in SSc-ILD. We sought to define the transcriptome and chromatin structural changes of SPP1 SSc-ILD macrophages, so as to better understand their role in promoting fibrosis and to identify transcription factors associated with open chromatin driving their altered phenotype.

2022-09-02 | GSE212109 | GEO

Epigenetic regulation of profibrotic macrophages in systemic sclerosis- associated interstitial lung disease

Project description:Epigenetic regulation of profibrotic macrophages in systemic sclerosis- associated interstitial lung disease

| PRJNA874032 | ENA

Evaluation of common profibrotic pathway across interstitial lung disease

Project description:Evaluation of common profibrotic pathway across interstitial lung disease

| PRJNA967318 | ENA

Evaluation of common profibrotic pathway across interstitial lung disease

Project description:Given that the etiology and clinical manifestations differ substantially between IPF and SSc-ILD, we sought to better understand the similarities and differences in various profibrotic pathways of interest.

2023-07-26 | GSE231693 | GEO

Duke CC

Project description:Duke CIVICs Clinical Core (Duke CC)

| PRJNA1055131 | ENA