Activation of fibroblastic reticular cells in kidney lymph node during crescentic glomerulonephritis

Abstract

Crescentic glomerulonephritis is an inflammatory condition characterized by rapid deterioration of kidney function. Previous studies of crescentic glomerulonephritis have focused on immune activation in the kidney. However, the role of fibroblastic reticular cells, which reside in the stromal compartment of the kidney lymph node, has not been studied in this condition. We investigated the activation of kidney lymph node-resident fibroblastic reticular cells in nephrotoxic serum nephritis, a classic murine model of crescentic glomerulonephritis. We found that increased deposition of extracellular matrix fibers by fibroblastic reticular cells in the kidney lymph node was associated with the propagation of high endothelial venules, specialized blood vessels through which lymphocytes enter the lymph node, as well as with expansion of the lymphatic vasculature. The kidney lymph node also contained an expanding population of pro-inflammatory T cells. Removal of the kidney lymph node, depletion of fibroblastic reticular cells, and treatment with anti-podoplanin antibody each resulted in reduction of kidney injury. Our findings suggest that modulating the activity of fibroblastic reticular cells may be a novel therapeutic approach in crescentic glomerulonephritis.

Keywords: Goodpasture syndrome; acute kidney injury; anti–glomerular basement membrane disease; glomerulonephritis; lymphocyte.