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Updated: May 28, 2026
Adoptive Transfer of IL-33-Stimulated Macrophages into Bleomycin-Induced Mouse Models to Study Their Effect on Idiopathic Pulmonary Fibrosis In Vivo
Published on: May 5, 2023
Integrated Single-Cell and Bulk RNA Sequencing Identifies Macrophage Heterogeneity and Mitophagy-Related Biomarkers
1School of Qihuang Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
Abstract:
Mitophagy clears damaged mitochondria and maintains normal macrophage function. Clarifying the associations between idiopathic pulmonary fibrosis (IPF), macrophages, and mitophagy is crucial for early diagnosis and clinical management. Core macrophage subsets were identified as M2 macrophages via single-cell RNA sequencing and immune infiltration analysis. Differentially expressed genes related to this subset were obtained. Integrated differential expression analysis, weighted gene co-expression network analysis, machine learning, and expression verification were applied to screen biomarkers. CD163 and SPP1 were identified through biomarker screening, both showing significantly increased expression in IPF. Functional enrichment showed that these biomarkers are mainly involved in cell cycle checkpoints and ciliopathies. Immune microenvironment analysis identified 16 immune cell types with significant differences between IPF and control groups, among which T helper 2 cells were strongly positively correlated with CD163. A total of nine drugs were found to be associated with CD163 and SPP1. The expression of these biomarkers changed dynamically during M2 macrophage differentiation. This study integrates single-cell and bulk transcriptomics analysis to reveal the critical roles of CD163 and SPP1 in the IPF macrophage-mitochondrial autophagy axis, a novel framework for understanding the macrophage-mitophagy axis in IPF pathogenesis.
Insights
Idiopathic pulmonary fibrosis (IPF) involves M2 macrophages and mitophagy. Researchers identified CD163 and SPP1 as key biomarkers, offering new insights into IPF pathogenesis and potential therapeutic targets.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Mitophagy is essential for macrophage function and clearing damaged mitochondria.
- Understanding the interplay between idiopathic pulmonary fibrosis (IPF), macrophages, and mitophagy is critical for diagnosis and treatment.
- M2 macrophages play a significant role in the IPF immune microenvironment.
Purpose of the Study:
- To identify biomarkers associated with IPF pathogenesis within the macrophage-mitophagy axis.
- To investigate the role of specific macrophage subsets, particularly M2 macrophages, in IPF.
- To explore potential therapeutic targets by analyzing drug associations with identified biomarkers.
Main Methods:
- Single-cell RNA sequencing and immune infiltration analysis to identify M2 macrophages.
- Integrated differential expression analysis, weighted gene co-expression network analysis, and machine learning for biomarker screening.
- Expression verification and immune microenvironment analysis to assess biomarker relevance and cellular correlations.
Main Results:
- CD163 and SPP1 were identified as significantly upregulated biomarkers in IPF, linked to cell cycle checkpoints and ciliopathies.
- M2 macrophages and T helper 2 cells were prominent in the IPF immune microenvironment, with CD163 positively correlated with T helper 2 cells.
- Nine drugs were found to be associated with the identified biomarkers, suggesting potential therapeutic interventions.
Conclusions:
- CD163 and SPP1 are critical players in the IPF macrophage-mitophagy axis.
- This study provides a novel framework for understanding macrophage-mitophagy in IPF.
- The identified biomarkers and associated drugs offer potential avenues for IPF diagnosis and treatment.
