Abstract: TH-PO0980
Immune Surveillance of Urinary Antigens Drives T-Cell Activation in the Kidneys
Session Information
- Transplantation: Basic - Immune Biology, Tissue Injury, and Emerging Technologies
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2001 Transplantation: Basic
Authors
- Elias, Esteban E., University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
- Lau, Arthur, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
- Belay, Sisay G., University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
- Chappellaz, Mona L., University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
- Andonegui, Graciela, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
- Hutchens, Michael, Portland VA Medical Center, Portland, Oregon, United States
- Bracey, Nathan, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
- Chun, Justin, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
- Muruve, Daniel A., University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
Background
The mechanisms governing primary immune responses in the kidney are poorly understood. The renal interstitium harbors resident macrophages and dendritic cells (rMDC) with features of professional antigen-presenting cells, but how antigens are handled and shape adaptive immune responses in the kidney is not well understood. We tested the hypothesis that proximal tubular transport of filtered protein antigens facilitates their uptake into MHCII+ rMDCs to promote antigen-specific T-cell activation and renal inflammation.
Methods
Antigen trafficking in vivo was examined using labelled ovalbumin (OVA) administered to Cx3cr1(GFP/+), proximal tubule Lrp2 deficient Lrp2(fl/fl)Ndrg1(CreERT2/+), and C57BL/6 mice receiving the inhibitor cilastatin. CD4+ T cell responses were assessed in T-cell receptor transgenic OT-II and OT-II Lrp2(fl/fl)Ndrg1(CreERT2/+) mice receiving OVA antigen. rMDC activation was induced by renal ischemia/reperfusion injury. Antigen trafficking and immune responses were analyzed by intravital microscopy, flow cytometry, single cell and spatial transcriptomics.
Results
A network of rMDCs closely interacting with renal vasculature and tubules expressed a phenotype of potential antigen presenting cells. After systemic OVA administration, tubules reabsorbed filtered antigen, while rMDCs acquired OVA from peritubular capillaries and proximal tubules. CD45+CD11c+MHCII+ rMDCs showed greater OVA uptake than liver and spleen DCs in vivo, despite comparable uptake in vitro. Cilastatin blocked LRP2-mediated antigen reabsorption, reducing OVA uptake in tubules and rMDCs. OVA trafficking was reduced in Lrp2(fl/fl)Ndgr1 mice confirming that LRP2 mediates tubular antigen transport and uptake into rMDCs. Following ischemia/reperfusion, rMDCs were activated and upregulated CD86 and genes associated with antigen-presentation. In OT-II mice, OVA and rMDC activation triggered tubulointerstitial inflammation with a predominant Th1 CD4+ T cell immune response, which was reduced by cilastatin and attenuated in OT-II Lrp2(fl/fl) Ndrg1(CreERT2/+) mice.
Conclusion
These findings support a model in which LRP2-dependent transport increases antigen availability and uptake by kidney rMDC enabling an immune surveillance capability for filtered antigens in the proximal tubular lumen. The reabsorption of filtered antigens is functional and drives antigen-specific CD4+ T-cell immune responses in the kidney.
Acknowledgment
This research was supported by a project grant from the Canadian Institutes of Health Research.
Funding
- Government Support – Non-U.S.