Abstract: FR-PO1231
CAPG Promotes Renal Fibrosis by Regulating γδ T Cells
Session Information
- CKD: Mechanisms, AKI, and Beyond - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Zhang, Meng, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Chen, Sixiu, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Liang, Zhaoxin, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Chen, Wei, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
Background
Renal fibrosis is the final manifestation of chronic kidney disease regardless of etiology. γδ T cells are characterized by unique TCR composition (γ and δ chains) and play an important role in organs fibrosis. However, the relationship between γδ T cells and renal fibrosis and its molecular mechanism are poorly defined. Our study aimed to elucidate the regulatory role of Capping Actin Protein, Gelsolin Like (CAPG) in γδ T cell-driven renal fibrosis.
Methods
Murine models of renal fibrosis were established via unilateral ureteral obstruction (UUO) and folic acid (FA). Single-cell RNA sequencing (scRNA-seq) was performed on FA-induced fibrotic kidneys. We generated Capg knockout (Capg-/-) and Wild type (Capg+/+) mice and utilized FA and UUO models. Further, γδ T cells isolated from UUO kidneys of Capg+/+ mice were adoptively transferred into Capg-/- mice via tail vein, followed by UUO. Kidney sections were subjected to renal histopathological, flow cytometry, Western blotting, immunofluorescence (IF).
Results
scRNA-seq demonstrated a progressive upregulation of CAPG expression level in T lymphocytes correlating with renal fibrosis severity. After dimensionality reduction cluster analysis of T cell subsets, CAPG was primarily expressed in γδ T cells and Treg cells, with γδ T cell-specific CAPG levels escalating in parallel with fibrosis progression. Flow cytometry exhibited γδ T cells activation in FA- and UUO-induced renal fibrosis, and confirmed CAPG predominantly expressed in γδ T cells compared to CD4+ T cells, CD8+ T cells, double-negative T cells, with significantly elevated CAPG levels in γδ T cells from fibrotic kidney compared to controls. IF revealed co-localization of γδ T cells and CAPG. Knockout of CAPG significantly attenuated renal fibrosis, reduced extracellular matrix deposition, downregulated expression of fibrotic markers, and decreased γδ T cells infiltration. During renal fibrosis, γδT cells predominantly exhibited γδT17 phenotype characterized by IL-17A secretion, which was substantially reduced upon CAPG deletion. The adoptive transfer of γδ T cells partially reversed the anti-fibrotic effects of Capg -/- mice in the process of renal fibrosis.
Conclusion
γδ T cells are activated in response to renal fibrosis. High CAPG expression in γδ T cells is associated with their activation and IL-17A secretion. CAPG is a potential therapeutic target for γδ T cell-mediated renal fibrosis.
Funding
- Government Support – Non-U.S.