Title: Cross Dendritic Cells Anger T Cells after Kidney Injury
Abstract: Nearly 30 yr ago, Stewart Cameron caused a minor revolution by pointing out that simple quantitation of proteinuria was much better at predicting outcome than histopathological diagnosis—then the gold standard prognostic marker.1 We now know that severe proteinuria does not simply reflect glomerular injury but is itself harmful.2 Reabsorption of large amounts of protein from the glomerular filtrate induces stress responses in proximal tubular epithelial cells that result in lysosomal instability and can even initiate epithelial-mesenchymal transition.3 Epithelial cells synthesize chemokines, cytokines, and complement components that recruit inflammatory cells and lymphocytes into the interstitium causing progressive fibrosis. A fascinating paper by Macconi et al. from Ariela Benigni's group in the current issue of JASN4 adds another layer of complexity by showing that albumin reabsorbed from proximal tubules induces the generation of albumin-specific, IFN-γ secreting, CD8 T cells that may contribute to progressive renal injury.
Before discussing the results in detail, it is important to consider how proteins reabsorbed by the proximal tubule are presented to T cells. The interstitium of normal kidneys contain numerous resident monocytic myelocytes, traditionally believed to be macrophages because they express relevant markers such as F4/80 in mice and CD68 in man.5 It is now known they also express dendritic cell markers and can indeed present antigen—one of the defining features of renal dendritic cells with …