Conventional Type 1 Dendritic Cells (cDC1) in Human Kidney Diseases: Clinico-Pathological Correlations

Background cDC1 is a subset of conventional DCs, whose most recognized function is cross-presentation to CD8(+) T cells. We conducted this study to investigate the number and location of cDC1s in various human kidney diseases as well as their correlation with clinico-pathological features and CD8(+) T cells. Methods We analyzed 135 kidney biopsies samples. Kidney diseases included: acute tubular necrosis (ATN), acute interstitial nephritis (AIN), proliferative glomerulonephritis (GN) (IgA nephropathy, lupus nephritis, pauci-immune GN, anti-GBM disease), non-proliferative GN (minimal change disease, membranous nephropathy) and diabetic nephropathy. Indirect immunofluorescence staining was used to quantify cDC1s, CD1c(+) DCs, and CD8(+) T cells. Results cDC1s were rarely present in normal kidneys. Their number increased significantly in ATN and proliferative GN, proportionally much more than CD1c(+) DCs. cDC1s were mainly found in the interstitium, except in lupus nephritis, pauci-immune GN and anti-GBM disease, where they were prominent in glomeruli and peri-glomerular regions. The number of cDC1s correlated with disease severity in ATN, number of crescents in pauci-immune GN, interstitial fibrosis in IgA nephropathy and lupus nephritis, as well as prognosis in IgA nephropathy. The number of CD8(+) T cells also increased significantly in these conditions and cDC1 number correlated with CD8(+) T cell number in lupus nephritis and pauci-immune GN, with many of them closely co-localized. Conclusions cDC1 number correlated with various clinic-pathological features and prognosis reflecting a possible role in these conditions. Their association with CD8(+) T cells suggests a combined mechanism in keeping with the results in animal models.

Automated summary

In human kidney diseases, cDC1 numbers significantly increase in acute tubular necrosis and proliferative glomerulonephritis, mainly located in the interstitium but also in the glomeruli in certain conditions. The number of cDC1s correlates with disease severity, pathological features, and prognosis, while also showing an association with CD8(+) T cell numbers in lupus nephritis and pauci-immune GN.