Localization and Regulation of Polymeric Ig Receptor in Healthy and Diseased Human Kidney
Localization and Regulation of Polymeric Ig Receptor in Healthy and Diseased Human Kidney
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DOI：
10.1016/j.ajpath.2019.06.015
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发表时间：
2019-10-01
影响因子：
6
通讯作者：
Johansson, Martin E.
中科院分区：
文献类型：
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作者：
Krawczyk, Krzysztof M.;Nilsson, Helen;Johansson, Martin E.
多聚体IG受体（PIgR）通过介导二聚体伊加转胞吞进入粘膜液而构成免疫系统的重要部分。尽管在器官如肠中进行了充分的研究，但PIgR在人肾脏中的调节和定位的特征并不完全。在此，使用免疫组织化学，我们表明，在健康的人肾脏，PIgR表达的祖细胞样肾小管散在细胞的近端小管和壁上皮细胞的肾小球。我们进一步表明，近端肾小管表达PIgR在肾脏疾病中变得广泛，与尿分泌伊加水平升高相关。尿分泌型伊加水平也与肾小管纤维化程度、血浆肌酐和尿素水平相关。此外，还体外培养了原代肾小管细胞，以研究PIgR的功能和调节。细胞PIgR表达诱导条件培养基从活化的人白细胞，以及炎症细胞因子，而转化生长因子β 1引起的表达下降。此外，干扰素-γ在培养的肾小管细胞中增加了二聚体伊加的转胞吞作用。最后，来自基因型-组织表达门户的mRNA数据的相关性研究表明，肾脏中的PIGR mRNA表达与TNFSF 13的表达相关，TNFSF 13是一种参与浆细胞类别转换为伊加的细胞因子。这些结果表明，PIgR诱导是肾小管细胞损伤表型的组成部分。
The polymeric Ig receptor (PIgR) constitutes an important part of the immune system by mediating transcytosis of dimeric IgA into mucosal fluids. Although well studied in organs such as the intestine, the regulation and localization of PIgR in human kidney are incompletely characterized. Herein, using immunohistochemistry, we show that in healthy human kidneys, PIgR is expressed by the progenitor-like tubular scattered cells of the proximal tubules and by parietal epithelial cells of glomeruli. We further show that proximal tubular expression of PIgR becomes widespread during kidney disease, correlating to elevated levels of urinary secretory IgA. Urinary secretory IgA levels also correlated to the degree of tubular fibrosis, plasma creatinine, and urea levels. In addition, primary tubular cells were cultured to study the function and regulation of PIgR in vitro. Cellular PIgR expression was induced by conditioned medium from activated human leukocytes, as well as by inflammatory cytokines, whereas transforming growth factor-beta 1 caused decreased expression. Furthermore, interferon-gamma increased the transcytosis of dimeric IgA in cultured tubular cells. Finally, a correlation study of mRNA data from the Genotype-Tissue Expression portal indicated that PIGR mRNA expression in kidney correlates to the expression of TNFSF13, a cytokine involved in plasma cell class switching to IgA. These results indicate that PIgR induction is an integral part of the injury phenotype of renal tubular cells.