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CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited nephropathy. To date, therapies alleviating the disease have largely focused on targeting abnormalities in renal epithelial cell signaling. ADPKD has many hallmarks of cancer, where targeting T cells has brought nov...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319903/ https://www.ncbi.nlm.nih.gov/pubmed/30249452 http://dx.doi.org/10.1016/j.kint.2018.06.025 |
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author | Kleczko, Emily K. Marsh, Kenneth H. Tyler, Logan C. Furgeson, Seth B. Bullock, Bonnie L. Altmann, Christopher J. Miyazaki, Makoto Gitomer, Berenice Y. Harris, Peter C. Weiser-Evans, Mary C.M. Chonchol, Michel B. Clambey, Eric T. Nemenoff, Raphael A. Hopp, Katharina |
author_facet | Kleczko, Emily K. Marsh, Kenneth H. Tyler, Logan C. Furgeson, Seth B. Bullock, Bonnie L. Altmann, Christopher J. Miyazaki, Makoto Gitomer, Berenice Y. Harris, Peter C. Weiser-Evans, Mary C.M. Chonchol, Michel B. Clambey, Eric T. Nemenoff, Raphael A. Hopp, Katharina |
author_sort | Kleczko, Emily K. |
collection | PubMed |
description | Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited nephropathy. To date, therapies alleviating the disease have largely focused on targeting abnormalities in renal epithelial cell signaling. ADPKD has many hallmarks of cancer, where targeting T cells has brought novel therapeutic interventions. However, little is known about the role and therapeutic potential of T cells in ADPKD. Here, we used an orthologous ADPKD model, Pkd1 p.R3277C (RC), to begin to define the role of T cells in disease progression. Using flow cytometry, we found progressive increases in renal CD8(+) and CD4(+) T cells, correlative with disease severity, but with selective activation of CD8(+) T cells. By immunofluorescence, T cells specifically localized to cystic lesions and increased levels of T-cell recruiting chemokines (CXCL9/CXCL10) were detected by qPCR/in situ hybridization in the kidneys of mice, patients, and ADPKD epithelial cell lines. Importantly, immunodepletion of CD8(+) T cells from one to three months in C57Bl/6 Pkd1(RC/RC) mice resulted in worsening of ADPKD pathology, decreased apoptosis, and increased proliferation compared to IgG-control, consistent with a reno-protective role of CD8(+) T cells. Thus, our studies suggest a functional role for T cells, specifically CD8(+) T cells, in ADPKD progression. Hence, targeting this pathway using immune-oncology agents may represent a novel therapeutic approach for ADPKD. |
format | Online Article Text |
id | pubmed-6319903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-63199032019-01-04 CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression Kleczko, Emily K. Marsh, Kenneth H. Tyler, Logan C. Furgeson, Seth B. Bullock, Bonnie L. Altmann, Christopher J. Miyazaki, Makoto Gitomer, Berenice Y. Harris, Peter C. Weiser-Evans, Mary C.M. Chonchol, Michel B. Clambey, Eric T. Nemenoff, Raphael A. Hopp, Katharina Kidney Int Article Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited nephropathy. To date, therapies alleviating the disease have largely focused on targeting abnormalities in renal epithelial cell signaling. ADPKD has many hallmarks of cancer, where targeting T cells has brought novel therapeutic interventions. However, little is known about the role and therapeutic potential of T cells in ADPKD. Here, we used an orthologous ADPKD model, Pkd1 p.R3277C (RC), to begin to define the role of T cells in disease progression. Using flow cytometry, we found progressive increases in renal CD8(+) and CD4(+) T cells, correlative with disease severity, but with selective activation of CD8(+) T cells. By immunofluorescence, T cells specifically localized to cystic lesions and increased levels of T-cell recruiting chemokines (CXCL9/CXCL10) were detected by qPCR/in situ hybridization in the kidneys of mice, patients, and ADPKD epithelial cell lines. Importantly, immunodepletion of CD8(+) T cells from one to three months in C57Bl/6 Pkd1(RC/RC) mice resulted in worsening of ADPKD pathology, decreased apoptosis, and increased proliferation compared to IgG-control, consistent with a reno-protective role of CD8(+) T cells. Thus, our studies suggest a functional role for T cells, specifically CD8(+) T cells, in ADPKD progression. Hence, targeting this pathway using immune-oncology agents may represent a novel therapeutic approach for ADPKD. 2018-09-21 2018-12 /pmc/articles/PMC6319903/ /pubmed/30249452 http://dx.doi.org/10.1016/j.kint.2018.06.025 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Kleczko, Emily K. Marsh, Kenneth H. Tyler, Logan C. Furgeson, Seth B. Bullock, Bonnie L. Altmann, Christopher J. Miyazaki, Makoto Gitomer, Berenice Y. Harris, Peter C. Weiser-Evans, Mary C.M. Chonchol, Michel B. Clambey, Eric T. Nemenoff, Raphael A. Hopp, Katharina CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression |
title | CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression |
title_full | CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression |
title_fullStr | CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression |
title_full_unstemmed | CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression |
title_short | CD8(+) T cells modulate autosomal dominant polycystic kidney disease progression |
title_sort | cd8(+) t cells modulate autosomal dominant polycystic kidney disease progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319903/ https://www.ncbi.nlm.nih.gov/pubmed/30249452 http://dx.doi.org/10.1016/j.kint.2018.06.025 |
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