Abstract: SA-PO1046
Vascular Injury-Derived Exosomes Trigger Renal Tertiary Lymphoid Structures and Accelerate Lupus Nephritis
Session Information
- Pathology and Lab Medicine - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Normand, Marie-Hélène, Universite de Montreal, Montreal, Quebec, Canada
- Juillard, Sandrine, Universite de Montreal, Montreal, Quebec, Canada
- Patey, Natalie, Chu Sainte Justine, Montreal, Quebec, Canada
- Boilard, Eric, Universite Laval, Quebec, Quebec, Canada
- Dieudé, Mélanie, Universite de Montreal, Montreal, Quebec, Canada
Background
Microvascular damage is an emerging contributing factor to Lupus Nephritis (LN) leading to end stage renal disease. We have demonstrated that apoptotic exosomes derived from vascular injury (ApoExo) trigger the production of SLE-associated antibodies in wild-type mice. ApoExo infusion induces autantibody production and tertiary lymphoid structure (TLS) formation in a murine vascular allograft rejection model. We hypothesize that ApoExo induce an autoimmune response that accelerates the development of lupus nephritis.
Methods
20 weeks old NZB/WF1 mice were infused with ApoExo or vehicle every second day for 3 weeks. Circulating anti-LG3 and ApoExo levels were measured by ELISA and hs-FCM respectively. Kidneys were collected and renal histology and 3D in vivo micro-computed tomography (MicroCT) analyses were performed.
Results
NZB/WF1 mice infused with ApoExo show higher levels of circulating anti-LG3 compared with the vehicle group (p=0.0034). MicroCT data suggest microvascular involution associated with LN development. In addition, ApoExo infused NZB/WF1 mice demonstrate significant renal inflammatory infiltration compared to mice infused with vehicle. ApoExo triggered the recruitment to the renal interstitium of CD3+, CD20+, and AID+ lymphocytes into nodules reminiscent of TLS (p=0.0342) associated with increased Lyve 1+ suggesting lymphoangiogenisis. Finally, heightened renal tubular damage (p<0.05), blood urea nitrogen levels (p<0.05) and decreased survival (p=0.0055) were observed in ApoExo infused NZB/WF1 mice compared to the ones infused with vehicle.
Conclusion
ApoExo infusion increases renal nodular lymphocyte infiltration, autoantibody production increase renal damage in lupus prone mice. This project is, to our knowledge, the first to evaluate the contribution of vascular injury derived extracellular vesicles to LN.
Funding
- Private Foundation Support