Kidney Week

Abstract: TH-PO0313

IFNα-Induced CD169+ Macrophages Drive Inflammation via the CCL2/NLRP3 Axis in IgAN: Transcriptomics and Functional Characterization

Session Information

• Glomerular Diseases: Omics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Song, Jiarong, The Second Xiangya Hospital of Central South University Department of Nephrology, Changsha, Hunan, China

Jiarong Song, MD, MS

• Li, Yifu, The Second Xiangya Hospital of Central South University Department of Nephrology, Changsha, Hunan, China

Yifu Li, MD, PhD

Background

CD169⁺ macrophages are emerging as key immunoregulatory cells in inflammatory and metabolic diseases, but their role in IgA nephropathy (IgAN) remains unclear. This study characterized IFNα induced CD169⁺ macrophages and examined how CD169 suppression modulates IgAN-related inflammatory pathways.

Methods

THP-1 derived macrophages were polarized into a CD169⁺ phenotype by stimulation with IFNα (25 ng/mL for 48 h). CD169⁺ and CD169⁻ macrophage subsets were isolated by fluorescence-activated cell sorting (FACS) and subjected to RNA sequencing (RNA-seq). Differentially expressed genes (DEGs) were identified using the criteria log₂ fold change > 2, Q-value < 0.05, and average TPM > 2 in both groups. KEGG pathway enrichment analysis, hierarchical clustering, and protein-protein interaction (PPI) network analyses were performed on the DEGs. For functional validation, CD169 expression was silenced using siRNA prior to IFNα stimulation. Cells were then stimulated with or without LPS (1 μg/mL for 6 h). Protein levels of CCL2, IL-1β, NLRP3, and NRF2 were quantified by Western blotting. Statistical analyses were performed using one-way ANOVA.

Results

Transcriptomic analysis identified 59 significantly DEGs between CD169⁺ and CD169⁻ macrophages. KEGG enrichment analysis revealed involvement of cholesterol metabolism, PPAR signaling, IL-17 signaling, cytokine-cytokine receptor interaction, and chemokine signaling pathways. Hierarchical clustering further identified 12 IgAN-related core DEGs, with PPI network analysis highlighting CCL2 as a central hub gene. Functionally, CD169 knockdown increased CCL2 expression and reduced NRF2 levels under basal conditions. Following LPS stimulation, CD169 silencing further enhanced CCL2, IL-1β, and NLRP3 expression while causing additional NRF2 suppression, indicating that CD169 negatively regulates macrophage inflammation and NLRP3 inflammasome activation.

Conclusion

IFNα induced CD169⁺ macrophages exhibit a unique transcriptomic profile enriched in inflammatory and metabolic pathways linked to IgAN. CD169 suppresses macrophage inflammation by inhibiting the CCL2/NLRP3 axis and maintaining NRF2 expression. CD169 loss induces a hyperinflammatory state with increased CCL2, IL-1β, and NLRP3 and reduced NRF2. These findings identify CD169 as a protective regulator and potential therapeutic target in IgAN.