%0 Journal Article
%T BowmanĄŻs capsule provides a protective niche for podocytes from cytotoxic CD8+ T cells
%A Anqun Chen
%A Chengguo Wei
%A Detlef Schlondorff
%A Jia Fu
%A John Cijiang He
%A Judith Agudo
%A Kyung Lee
%A Tian-Jun Guan
%A Vivette D. DĄŻAgati
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI97879
%X T cells play a key role in immune-mediated glomerulonephritis, but how cytotoxic T cells interact with podocytes remains unclear. To address this, we injected EGFP-specific CD8+ T cells from just EGFP death inducing (Jedi) mice into transgenic mice with podocyte-specific expression of EGFP. In healthy mice, Jedi T cells could not access EGFP+ podocytes. Conversely, when we induced nephrotoxic serum nephritis (NTSN) and injected Jedi T cells, EGFP+ podocyte transgenic mice showed enhanced proteinuria and higher blood urea levels. Morphometric analysis showed greater loss of EGFP+ podocytes, which was associated with severe crescentic and necrotizing glomerulonephritis. Notably, only glomeruli with disrupted BowmanĄŻs capsule displayed massive CD8+ T cell infiltrates that were in direct contact with EGFP+ podocytes, causing their apoptosis. Thus, under control conditions with intact BowmanĄŻs capsule, podocytes are not accessible to CD8+ T cells. However, breaches in BowmanĄŻs capsule, as also noted in human crescentic glomerulonephritis, allow access of CD8+ T cells to the glomerular tuft and podocytes, resulting in their destruction. Through these mechanisms, a potentially reversible glomerulonephritis undergoes an augmentation process to a rapidly progressive glomerulonephritis, leading to end-stage kidney disease. Translating these mechanistic insights to human crescentic nephritis should direct future therapeutic interventions at blocking CD8+ T cells, especially in progressive stages of rapidly progressive glomerulonephritis
%U https://www.jci.org/articles/view/97879