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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Autoimmune glomerulonephritis (GN), including lupus nephritis, ANCA-associated GN, and IgA nephropathy, is a major cause of end-stage renal disease. Although kidney injury in GN centers on immune complex-mediated sustained inflammation, the precise mechanisms driving local inflammatory activation, particularly the role of cathepsin S (CTSS), remain elusive. This study aims to investigate the cellular source, functional mechanism of CTSS in autoimmune GN, and validate its potential as a therapeutic target.
Renal transcriptomic datasets, tissue sections, and plasma samples from patients with various autoimmune GN were analyzed to establish the clinical relevance of CTSS. The nephrotoxic serum nephritis (NTN) and ovalbumin-immune complex (Ova-IC)-induced kidney inflammation model were further established in wild-type (WT), CTSS-deficient (Ctss-/-), CTSS-overexpressing (AAV-Ctss), and macrophage-specific CTSS knockout (Ctss△Lyz2) mice to define the role of CTSS in GN progression. Single-cell RNA sequencing (scRNA-seq) was performed on renal infiltrating cells to characterize immune populations and cell-cell communication. This was combined with in vitro macrophage-neutrophil co-culture experiments, recombinant CTSS/CXCL2 protein reconstitution, and application of the CTSS inhibitor LY3000328 to dissect the molecular pathway driving renal inflammation and its clinical translational potential.
Clinical cohort data showed that CTSS levels were significantly elevated in the kidneys and plasma of patients with autoimmune GN (including lupus nephritis, ANCA-associated GN, IgA nephropathy) and positively correlated with disease severity. In GN mouse models, either global or macrophage-specific CTSS deletion markedly attenuated disease manifestations, including proteinuria, renal dysfunction (elevated blood urea nitrogen and serum creatinine), histological damage, and infiltration of inflammatory cells particularly neutrophils. Conversely, CTSS overexpression exacerbated renal injury. scRNA-seq revealed macrophages as the primary contributors to renal CTSS and uncovered CTSS-dependent communication between macrophages and neutrophils. Mechanistic investigations demonstrated that macrophage-secreted CTSS acted extracellularly to promote neutrophil-derived CXCL2 production, establishing a self-amplifying, positive-feedback loop that fueled further neutrophil recruitment and renal accumulation. Finally, specific inhibition of CTSS significantly delayed disease progression in GN mice.
Our findings demonstrate that macrophage-derived CTSS, via its non-canonical secretory protease activity, initiates a "macrophage-CTSS-neutrophil-CXCL2" positive-feedback circuit that drives sustained local inflammation in autoimmune GN. Targeted inhibition of CTSS effectively disrupts this pathway, providing a novel and clinically promising strategy for treating autoimmune GN, particularly neutrophil-mediated refractory cases.
