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

Abstract

BackgroundcDC1 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.MethodsWe 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.ResultscDC1s 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.ConclusionscDC1 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.

Causality between Peripheral Immune Cell Counts and Membranous Nephropathy: A Bidirectional Mendelian Randomization Study

“…Conventional dendritic cells type 1 (cDC1) represent a subset of dendritic cells that are primarily involved in cross-presentation to CD8 T cells. Several studies have indicated that the number of cDC1 is associated with the severity of various renal conditions, including acute tubular necrosis, the presence of crescents in immune-mediated glomerulonephritis, interstitial fibrosis in IgA nephropathy and lupus nephritis, as well as the prognosis of IgA nephropathy (Chen et al 2021). In immune-mediated glomerulonephritis, there is a robust correlation between the number of cDC1 and crescent formation.…”

Innate immunity in diabetic nephropathy: Pathogenic mechanisms and therapeutic targets

“…Besides, targeting the growth factors crucial for DC survival and function is another strategy. For instance, FMS (proto‐oncogene that encodes the tyrosine kinase transmembrane receptor for colony stimulating factor 1 receptor [CSF‐1R], therefore FMS is also called CSF‐1R)‐like tyrosine kinase 3 ligand inhibitor are shown to selectively deplete CD103 + DCs proportion and mitigate kidney damage through suppression of CD103 + DCs‐mediated CD8 + T cells activation 168,181 …”