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Localization and Regulation of Polymeric Ig Receptor in Healthy and Diseased Human Kidney

Krawczyk, Krzysztof M. LU ; Nilsson, Helén LU ; Nyström, Jenny ; Lindgren, David LU ; Leandersson, Karin LU ; Swärd, Karl LU and Johansson, Martin E. LU (2019) In American Journal of Pathology 189(10). p.1933-1944
Abstract

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... (More)

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.

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Contribution to journal
publication status
published
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in
American Journal of Pathology
volume
189
issue
10
pages
12 pages
publisher
American Society for Investigative Pathology
external identifiers
  • pmid:31404540
  • scopus:85072328256
ISSN
0002-9440
DOI
10.1016/j.ajpath.2019.06.015
language
English
LU publication?
yes
id
ba0dde2d-bc2c-44ae-a7cb-bc3ed2200e68
date added to LUP
2019-09-30 12:29:39
date last changed
2020-10-20 03:04:18
@article{ba0dde2d-bc2c-44ae-a7cb-bc3ed2200e68,
  abstract     = {<p>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.</p>},
  author       = {Krawczyk, Krzysztof M. and Nilsson, Helén and Nyström, Jenny and Lindgren, David and Leandersson, Karin and Swärd, Karl and Johansson, Martin E.},
  issn         = {0002-9440},
  language     = {eng},
  number       = {10},
  pages        = {1933--1944},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Localization and Regulation of Polymeric Ig Receptor in Healthy and Diseased Human Kidney},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2019.06.015},
  doi          = {10.1016/j.ajpath.2019.06.015},
  volume       = {189},
  year         = {2019},
}