School of Medicine, The University of Sydney, Camperdown, NSW, Australia.
Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia.
Front Immunol. 2021 May 12;12:635212. doi: 10.3389/fimmu.2021.635212. eCollection 2021.
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.
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.
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.
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.
cDC1 是传统树突状细胞的一个亚群,其最被认可的功能是将抗原交叉呈递给 CD8 T 细胞。我们进行这项研究,旨在调查 cDC1 在各种人类肾脏疾病中的数量和位置,以及它们与临床病理特征和 CD8 T 细胞的相关性。
我们分析了 135 例肾活检样本。肾脏疾病包括:急性肾小管坏死(ATN)、急性间质性肾炎(AIN)、增生性肾小球肾炎(IgA 肾病、狼疮性肾炎、少免疫性肾小球肾炎、抗肾小球基底膜病)、非增生性肾小球肾炎(微小病变性肾病、膜性肾病)和糖尿病肾病。采用间接免疫荧光染色法对 cDC1、CD1c 树突状细胞和 CD8 T 细胞进行定量分析。
cDC1 在正常肾脏中很少存在。它们在 ATN 和增生性 GN 中的数量显著增加,与 CD1c 树突状细胞相比增加的比例更高。cDC1 主要存在于间质中,除了在狼疮性肾炎、少免疫性肾小球肾炎和抗肾小球基底膜病中,它们在肾小球和肾小球旁区显著存在。cDC1 的数量与 ATN 中的疾病严重程度、少免疫性肾小球肾炎中的新月体数量、IgA 肾病和狼疮性肾炎中的间质纤维化以及 IgA 肾病中的预后相关。在这些情况下,CD8 T 细胞的数量也显著增加,cDC1 的数量与狼疮性肾炎和少免疫性肾小球肾炎中的 CD8 T 细胞数量相关,其中许多细胞紧密共定位。
cDC1 的数量与各种临床病理特征和预后相关,反映了它们在这些疾病中的可能作用。它们与 CD8 T 细胞的关联表明存在一种联合机制,与动物模型的结果一致。