Podocyte-specific knockout of the neonatal Fc receptor (FcRn) results in differential protection depending on the model of glomerulonephritis
Podocytes have been proposed to be antigen presenting cells (APCs). In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against glomerulonephritis. Since podocytes express FcRn, we sought to determine whether the absence of p...
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| description | Podocytes have been proposed to be antigen presenting cells (APCs). In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against glomerulonephritis. Since podocytes express FcRn, we sought to determine whether the absence of podocyte FcRn ameliorates immune-mediated disease. We examined MHCII and costimulatory markers expression in cultured wild type (WT) and FcRn knockout (KO) podocytes. Interferon gamma (IFNγ) induced MHCII expression in both WT and KO podocytes but did not change CD80 expression. Neither WT nor KO expressed CD86 or inducible costimulatory ligand (ICOSL) at baseline or with IFNγ. Using an antigen presentation assay, WT podocytes but not KO treated with immune complexes induced a modest increase in IL-2. Induction of the anti-glomerular basement membrane (anti-GBM) model resulted in a significant decrease in glomerular crescents in podocyte-specific FcRn knockout mouse (podFcRn KO) versus controls but the overall percentage of crescents was low. To examine the effects of the podocyte-specific FcRn knockout in a model with a longer autologous phase, we used the nephrotoxic serum nephritis (NTS) model. We found that the podFcRn KO mice had significantly reduced crescent formation and glomerulosclerosis compared to control mice. This study demonstrates that lack of podocyte FcRn is protective in immune mediated kidney disease that is dependent on an autologous phase. This study also highlights the difference between the anti-GBM model and NTS model of disease. |
| doi_str_mv | 10.1371/journal.pone.0230401 |
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In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against glomerulonephritis. Since podocytes express FcRn, we sought to determine whether the absence of podocyte FcRn ameliorates immune-mediated disease. We examined MHCII and costimulatory markers expression in cultured wild type (WT) and FcRn knockout (KO) podocytes. Interferon gamma (IFNγ) induced MHCII expression in both WT and KO podocytes but did not change CD80 expression. Neither WT nor KO expressed CD86 or inducible costimulatory ligand (ICOSL) at baseline or with IFNγ. Using an antigen presentation assay, WT podocytes but not KO treated with immune complexes induced a modest increase in IL-2. Induction of the anti-glomerular basement membrane (anti-GBM) model resulted in a significant decrease in glomerular crescents in podocyte-specific FcRn knockout mouse (podFcRn KO) versus controls but the overall percentage of crescents was low. To examine the effects of the podocyte-specific FcRn knockout in a model with a longer autologous phase, we used the nephrotoxic serum nephritis (NTS) model. We found that the podFcRn KO mice had significantly reduced crescent formation and glomerulosclerosis compared to control mice. This study demonstrates that lack of podocyte FcRn is protective in immune mediated kidney disease that is dependent on an autologous phase. This study also highlights the difference between the anti-GBM model and NTS model of disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0230401</identifier><identifier>PMID: 33370294</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibodies ; Antigen presentation ; Antigen-antibody complexes ; Antigen-presenting cells ; Antigens ; Biology and Life Sciences ; CD80 antigen ; CD86 antigen ; Cells, Cultured ; Cloning ; Dendritic cells ; Development and progression ; Disease Models, Animal ; Engineering and Technology ; Epithelial cells ; Experiments ; Fc receptors ; Flow Cytometry ; Genetic aspects ; Glomerular Basement Membrane - metabolism ; Glomerulonephritis ; Glomerulonephritis - genetics ; Glomerulonephritis - metabolism ; Health aspects ; Histocompatibility Antigens Class I - genetics ; Histocompatibility Antigens Class I - metabolism ; Hypertension ; Immune response ; Immune system ; Infants (Newborn) ; Interferon ; Interleukin 2 ; Kidney diseases ; Laboratory animals ; Lymphocytes ; Medical research ; Medicine ; Medicine and Health Sciences ; Mice ; Mice, Knockout ; Neonates ; Nephritis ; Nephrology ; Newborn babies ; Podocytes - metabolism ; Receptors ; Receptors, Fc - genetics ; Receptors, Fc - metabolism ; γ-Interferon</subject><ispartof>PloS one, 2020-12, Vol.15 (12), p.e0230401</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Dylewski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Dylewski et al 2020 Dylewski et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-7cf2663ad81b005b8d10b633fba1322e3c7cf6d9ae9dcaea2703d519e20a0d633</citedby><cites>FETCH-LOGICAL-c593t-7cf2663ad81b005b8d10b633fba1322e3c7cf6d9ae9dcaea2703d519e20a0d633</cites><orcidid>0000-0002-8158-8605</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769425/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769425/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33370294$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Jia, Zhanjun</contributor><creatorcontrib>Dylewski, James F</creatorcontrib><creatorcontrib>Tonsawan, Pantipa</creatorcontrib><creatorcontrib>Garcia, Gabriela</creatorcontrib><creatorcontrib>Lewis, Linda</creatorcontrib><creatorcontrib>Blaine, Judith</creatorcontrib><title>Podocyte-specific knockout of the neonatal Fc receptor (FcRn) results in differential protection depending on the model of glomerulonephritis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Podocytes have been proposed to be antigen presenting cells (APCs). In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against glomerulonephritis. Since podocytes express FcRn, we sought to determine whether the absence of podocyte FcRn ameliorates immune-mediated disease. We examined MHCII and costimulatory markers expression in cultured wild type (WT) and FcRn knockout (KO) podocytes. Interferon gamma (IFNγ) induced MHCII expression in both WT and KO podocytes but did not change CD80 expression. Neither WT nor KO expressed CD86 or inducible costimulatory ligand (ICOSL) at baseline or with IFNγ. Using an antigen presentation assay, WT podocytes but not KO treated with immune complexes induced a modest increase in IL-2. Induction of the anti-glomerular basement membrane (anti-GBM) model resulted in a significant decrease in glomerular crescents in podocyte-specific FcRn knockout mouse (podFcRn KO) versus controls but the overall percentage of crescents was low. To examine the effects of the podocyte-specific FcRn knockout in a model with a longer autologous phase, we used the nephrotoxic serum nephritis (NTS) model. We found that the podFcRn KO mice had significantly reduced crescent formation and glomerulosclerosis compared to control mice. This study demonstrates that lack of podocyte FcRn is protective in immune mediated kidney disease that is dependent on an autologous phase. 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metabolism</topic><topic>Glomerulonephritis</topic><topic>Glomerulonephritis - genetics</topic><topic>Glomerulonephritis - metabolism</topic><topic>Health aspects</topic><topic>Histocompatibility Antigens Class I - genetics</topic><topic>Histocompatibility Antigens Class I - metabolism</topic><topic>Hypertension</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Infants (Newborn)</topic><topic>Interferon</topic><topic>Interleukin 2</topic><topic>Kidney diseases</topic><topic>Laboratory animals</topic><topic>Lymphocytes</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neonates</topic><topic>Nephritis</topic><topic>Nephrology</topic><topic>Newborn babies</topic><topic>Podocytes - metabolism</topic><topic>Receptors</topic><topic>Receptors, Fc - genetics</topic><topic>Receptors, Fc - metabolism</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dylewski, James F</creatorcontrib><creatorcontrib>Tonsawan, Pantipa</creatorcontrib><creatorcontrib>Garcia, Gabriela</creatorcontrib><creatorcontrib>Lewis, Linda</creatorcontrib><creatorcontrib>Blaine, Judith</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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In traditional APCs, the neonatal Fc receptor (FcRn) is required for antigen presentation and global knockout of FcRn protects against glomerulonephritis. Since podocytes express FcRn, we sought to determine whether the absence of podocyte FcRn ameliorates immune-mediated disease. We examined MHCII and costimulatory markers expression in cultured wild type (WT) and FcRn knockout (KO) podocytes. Interferon gamma (IFNγ) induced MHCII expression in both WT and KO podocytes but did not change CD80 expression. Neither WT nor KO expressed CD86 or inducible costimulatory ligand (ICOSL) at baseline or with IFNγ. Using an antigen presentation assay, WT podocytes but not KO treated with immune complexes induced a modest increase in IL-2. Induction of the anti-glomerular basement membrane (anti-GBM) model resulted in a significant decrease in glomerular crescents in podocyte-specific FcRn knockout mouse (podFcRn KO) versus controls but the overall percentage of crescents was low. To examine the effects of the podocyte-specific FcRn knockout in a model with a longer autologous phase, we used the nephrotoxic serum nephritis (NTS) model. We found that the podFcRn KO mice had significantly reduced crescent formation and glomerulosclerosis compared to control mice. This study demonstrates that lack of podocyte FcRn is protective in immune mediated kidney disease that is dependent on an autologous phase. This study also highlights the difference between the anti-GBM model and NTS model of disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33370294</pmid><doi>10.1371/journal.pone.0230401</doi><orcidid>https://orcid.org/0000-0002-8158-8605</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-12, Vol.15 (12), p.e0230401 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2473448516 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animals Antibodies Antigen presentation Antigen-antibody complexes Antigen-presenting cells Antigens Biology and Life Sciences CD80 antigen CD86 antigen Cells, Cultured Cloning Dendritic cells Development and progression Disease Models, Animal Engineering and Technology Epithelial cells Experiments Fc receptors Flow Cytometry Genetic aspects Glomerular Basement Membrane - metabolism Glomerulonephritis Glomerulonephritis - genetics Glomerulonephritis - metabolism Health aspects Histocompatibility Antigens Class I - genetics Histocompatibility Antigens Class I - metabolism Hypertension Immune response Immune system Infants (Newborn) Interferon Interleukin 2 Kidney diseases Laboratory animals Lymphocytes Medical research Medicine Medicine and Health Sciences Mice Mice, Knockout Neonates Nephritis Nephrology Newborn babies Podocytes - metabolism Receptors Receptors, Fc - genetics Receptors, Fc - metabolism γ-Interferon |
| title | Podocyte-specific knockout of the neonatal Fc receptor (FcRn) results in differential protection depending on the model of glomerulonephritis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T08%3A56%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Podocyte-specific%20knockout%20of%20the%20neonatal%20Fc%20receptor%20(FcRn)%20results%20in%20differential%20protection%20depending%20on%20the%20model%20of%20glomerulonephritis&rft.jtitle=PloS%20one&rft.au=Dylewski,%20James%20F&rft.date=2020-12-28&rft.volume=15&rft.issue=12&rft.spage=e0230401&rft.pages=e0230401-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0230401&rft_dat=%3Cgale_plos_%3EA646874290%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2473448516&rft_id=info:pmid/33370294&rft_galeid=A646874290&rft_doaj_id=oai_doaj_org_article_9f996e43494044dfa18c58c904954624&rfr_iscdi=true |