Center for Molecular Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Am J Pathol. 2019 Oct;189(10):1933-1944. doi: 10.1016/j.ajpath.2019.06.015. Epub 2019 Aug 9.
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-β1 caused decreased expression. Furthermore, interferon-γ 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.
多聚免疫球蛋白受体 (PIgR) 通过介导二聚体 IgA 向黏膜液的转胞运输，构成免疫系统的重要组成部分。尽管在肠道等器官中得到了很好的研究，但 PIgR 在人肾脏中的调节和定位尚未完全描述。在此，我们通过免疫组织化学显示，在健康的人肾脏中，PIgR 由近端小管的祖细胞样散在细胞和肾小球的壁细胞表达。我们进一步表明，在肾脏疾病期间，近端小管中 PIgR 的表达变得广泛，与尿分泌型 IgA 水平升高相关。尿分泌型 IgA 水平也与肾小管纤维化、血浆肌酐和尿素水平的程度相关。此外，我们培养原代肾小管细胞以研究 PIgR 在体外的功能和调节。细胞 PIgR 表达可被激活的人白细胞条件培养基以及炎症细胞因子诱导，而转化生长因子-β1 则导致其表达降低。此外，干扰素-γ 增加了培养的肾小管细胞中二聚体 IgA 的转胞运输。最后，对 Genotype-Tissue Expression 门户的 mRNA 数据进行的相关性研究表明，肾脏中 PIGR mRNA 的表达与参与浆细胞向 IgA 类别转换的细胞因子 TNFSF13 的表达相关。这些结果表明，PIgR 的诱导是肾小管细胞损伤表型的一个组成部分。
