ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO1424

Immune Checkpoint Molecule BTLA Attenuates Inflammation and Glomerular Damage in Experimental Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Diefenhardt, Paul, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Brand, Marie, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Schömig, Thomas, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Trinsch, Bastian, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Schermer, Bernhard, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Brinkkoetter, Paul T., Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Benzing, Thomas, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Braehler, Sebastian, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
Background

An imbalance of pro- and anti-inflammatory signals in the kidney can result in irreversible damage and destruction of glomeruli leading to end stage kidney disease. Current treatment of the glomerulonephritis (GN) consists of unspecific, highly toxic immunosuppressive therapies with detrimental adverse effects. More specific therapies are therefore warranted. T Lymphocytes are not only key players in the nephrotoxic nephritis (NTN) model in rodents but also during GN in humans, representing potential targets for tailored therapies. As an immune checkpoint molecule, B and T lymphocyte attenuator (BTLA) is crucial in the regulation of T Lymphocyte activation and has been shown to mediate anti-inflammatory effects in other T cell-mediated disease models.

Methods

NTN was induced in BTLA knock out mice (BTLA-KO) and littermate controls. Regular urine analysis (ACR) was performed throughout the course of the disease. 14 days after NTN induction, blood, kidneys and spleens were harvested for further analysis. Histological assessment of the kidneys was used to evaluate the severity of NTN. Local immune response in the kidney and systemic immunity was analyzed via flow cytometry and qPCR.

Results

Wild type mice (WT) showed an increased BTLA expression on renal T cells and dendritic cells throughout the course of NTN. No immuno-phenotype was observed in unstimulated BTLA-KO and WT mice. However, BTLA-KO resulted in aggravation of NTN compared to WT. Quantification and characterization of renal immune cells revealed an increase in proinflammatory cells. Interestingly, especially T Lymphocytes were significantly expanded in BTLA-KO mice.

Conclusion

BTLA attenuates inflammation in experimental GN through suppression of proinflammatory T Lymphocytes. These results build the foundation of a checkpoint inhibitor based therapy of inflammatory glomerular disease.