Abstract: SA-PO0717
Integrated Spatial Proteomics and Single-Cell Analysis Identifies CCL2-CCR2 Axis as Central Mediator of Cellular Cross-Talk in IgAN
Session Information
- Glomerular Diseases: Profiling Through Multiomics
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Li, Diangeng, Capital Medical University Beijing Ditan Hospital, Beijing, China
- Jin, Meiling, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China
Background
Immunoglobulin A nephropathy (IgAN) is characterized by mesangial IgA deposition and inflammatory activation, but the spatial cellular interactions driving disease progression remain poorly understood.
Methods
We employed imaging mass cytometry (IMC)-based spatial proteomics to map the kidney microenvironment, combined with single-cell RNA sequencing (scRNA-seq) to dissect intercellular crosstalk at the transcriptional level.
Results
Our study identified activated mesangial cells as pivotal orchestrators of disease progression in IgA nephropathy, demonstrating their vital role in establishing robust cellular interactions with macrophages, T cell and B cell within the glomerular microenvironment. Through detailed spatial analysis, we uncovered activated mesangial cells actively secreted the chemokine CCL2, which specifically recruited CCR2-expressing macrophages to glomerular regions. These infiltrating macrophages subsequently released pro-inflammatory mediators CCL3 and CCL4, creating a feed-forward loop that further activated neighboring T and B cells. This coordinated cellular crosstalk resulted in progressive amplification of the local inflammatory response, establishing and sustaining a self-perpetuating pro-inflammatory microenvironment that drives glomerular injury in IgAN.
Conclusion
Our study uncovers a CCL2 and its receptor as a critical mechanism by which activated mesangial cells recruit macrophages, which in turn amplify T/B cell-driven inflammation. This work fundamentally advances our understanding of the cellular and molecular choreography underlying IgAN progression while providing concrete directions for therapeutic intervention.