Kidney Week

Abstract: TH-PO840

Modulation of Immune Response in Kidney Lymph Node During Crescentic Glomerulonephritis

Session Information

• Glomerular Diseases: Immunology and Inflammation - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Kasinath, Vivek, Brigham and Women's Hospital, Boston, Massachusetts, United States

Vivek Kasinath,

• Yilmam, Osman Arif, Brigham and Women's Hospital, Boston, Massachusetts, United States

Osman Arif Yilmam,

• Uehara, Mayuko, Brigham and Women's Hospital, Boston, Massachusetts, United States

Mayuko Uehara,

• Jiang, Liwei, Brigham and Women's Hospital, Boston, Massachusetts, United States

Liwei Jiang,

• Ordikhani, Farideh, Brigham and Women's Hospital, Boston, Massachusetts, United States

Farideh Ordikhani,

• Salant, David J., Boston University Medical Center, Boston, Massachusetts, United States

David J. Salant,

• Abdi, Reza, Brigham and Women's Hospital, Boston, Massachusetts, United States

Reza Abdi,

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