Abstract: TH-PO0672
CD169 Deficiency Exacerbates Tubular Injury and Macrophage Infiltration in a Mouse Model of IgAN
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 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
- Song, Jiarong, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Xiao, Haoliang, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mo, Jinyou, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Huang, Kunlin, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Li, Yifu, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
Background
In IgA nephropathy (IgAN), macrophage-driven inflammation and fibrosis are key pathological features. CD169+macrophages, which are critical for immune complex clearance and immune tolerance, may influence IgAN pathogenesis. However, their specific role in IgAN remains unclear. Understanding CD169's involvement could reveal novel therapeutic targets to control renal injury and preserve kidney function in IgAN.
Methods
CD169 knockout (CD169-/-) mice were generated using CRISPR-Cas9. IgAN models were established in wild-type and CD169-/-mice via oral mucosal immunization. IgA deposition was assessed by immunofluorescence, and renal pathology evaluated with HE and PAS staining. Immunohistochemistry for F4/80 and KIM-1 assessed macrophage infiltration and tubular injury. Western blot measured renal IL-6 and KIM-1 expression. Urine protein and serum creatinine levels were tested to evaluate renal function. Integrating tissue pathology, immune cell infiltration, and functional indicators helped elucidate CD169’s role in modulating tubular injury and the progression of IgAN.
Results
No spontaneous IgA deposition was observed in the CD169-/- mice, whereas mesangial IgA deposition was evident in the IgAN model group. There was no significant difference in IgA fluorescence intensity between the CD169-/--IgAN and WT-IgAN groups. In the WT-IgAN group, CD169 expression in the renal interstitium was significantly upregulated. Both IgAN groups exhibited glomerular mesangial hyperplasia, tubular abnormalities, and interstitial inflammatory cell infiltration. Compared with the WT-IgAN group, the CD169-/--IgAN group showed higher tubular KIM-1 expression (P<0.05), increased infiltration of F4/80+ macrophages in the renal interstitium (P<0.0001), and significantly elevated levels of IL-6 and KIM-1. Renal function analysis revealed a marked increase in urinary protein levels in the CD169-/--IgAN group (P<0.0001), while serum creatinine levels showed no significant difference.
Conclusion
In conclusion, our study shows CD169-/--IgAN mice have higher KIM-1, more F4/80+ macrophages, increased IL-6, and greater proteinuria than WT-IgAN mice. These results indicate CD169 deficiency worsens tubular injury and inflammation in IgAN. CD169 plays a protective role by limiting renal inflammation and damage. Its absence leads to worsened disease severity.