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: TH-PO840

Modulation of Immune Response in Kidney Lymph Node During Crescentic Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Kasinath, Vivek, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Yilmam, Osman Arif, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Uehara, Mayuko, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Jiang, Liwei, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Ordikhani, Farideh, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Salant, David J., Boston University Medical Center, Boston, Massachusetts, United States
  • Abdi, Reza, Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

Crescentic glomerulonephritis (GN) is an inflammatory condition characterized by a rapid deterioration of renal function. Previous studies of crescentic GN have focused on immune activation in the kidney. However, the role of fibroblastic reticular cells (FRCs), the prominent cells comprising the stromal compartment of the kidney lymph node (KLN), has not been studied in this condition.

Methods

We induced nephrotoxic serum nephritis (NTN), a classic experimental model of crescentic GN, in mice. We investigated the contribution of FRCs in the KLN to the activation of the immune response in crescentic GN using flow cytometry, RT-PCR, hematoxylin and eosin (H&E) staining, and immunofluorescence staining.

Results

Investigation of the microarchitecture of the KLN during NTN revealed an increase in the deposition of extracellular matrix fibers by FRCs, associated with the propagation of specialized blood vessels known as high endothelial venules, through which lymphocytes traffic into the lymph node, as well as the expansion of the lymphatic vasculature. The KLN contained an expanding population of pro-inflammatory CD4+ effector memory T cells and Th17 cells. Removal of the KLN, depletion of FRCs, and treatment with anti-podoplanin antibody each resulted in a reduction of renal injury.

Conclusion

The pro-inflammatory activity of FRCs in the KLN is crucial to the propagation of the immune response in crescentic GN. Our findings can serve as a basis for the development of immunosuppressive therapy for crescentic GN directed towards modulating the activity of FRCs.

Funding

  • NIDDK Support