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IFNγ-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4(+) T Cell Migration
Diabetogenic T cells infiltrate the pancreatic islets by transmigrating across the microcapillaries residing close to, or within, the pancreatic islets. Deficiency in IFNγ signaling prevents efficient migration of T cells into the pancreatic islets, but the IFNγ-regulated molecules that mediate this...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282031/ https://www.ncbi.nlm.nih.gov/pubmed/30555479 http://dx.doi.org/10.3389/fimmu.2018.02800 |
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author | Scott, Nicholas A. Zhao, Yuxing Krishnamurthy, Balasubramanian Mannering, Stuart I. Kay, Thomas W. H. Thomas, Helen E. |
author_facet | Scott, Nicholas A. Zhao, Yuxing Krishnamurthy, Balasubramanian Mannering, Stuart I. Kay, Thomas W. H. Thomas, Helen E. |
author_sort | Scott, Nicholas A. |
collection | PubMed |
description | Diabetogenic T cells infiltrate the pancreatic islets by transmigrating across the microcapillaries residing close to, or within, the pancreatic islets. Deficiency in IFNγ signaling prevents efficient migration of T cells into the pancreatic islets, but the IFNγ-regulated molecules that mediate this are uncertain. Homing of autoreactive T cells into target tissues may require antigen specificity through presentation of cognate antigen by MHC expressed on the vascular endothelium. We investigated the hypothesis that IFNγ promotes the migration of islet antigen-specific CD4(+) T cells by upregulating MHC class II on islet endothelial cells (IEC), thereby providing an antigen-specific signal for islet infiltration. Upon IFNγ stimulation, MHC class II, which is not constitutively expressed on IEC, was induced. IFNγ-dependent upregulation of MHC class II was detected in IEC isolated from prediabetic NOD mice at the earliest stages of insulitis, before other markers of inflammation were present. Using a CD4(+) T cell-mediated adoptive transfer model of autoimmune diabetes we observed that even though diabetes does not develop in recipient mice lacking IFNγ receptors, mice with MHC class II-deficient IEC were not protected from disease. Thus, IFNγ-regulated molecules, but not MHC class II or antigen presentation by IECs is required for the early migration of antigen-specific CD4(+) T cells into the pancreatic islets. |
format | Online Article Text |
id | pubmed-6282031 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62820312018-12-14 IFNγ-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4(+) T Cell Migration Scott, Nicholas A. Zhao, Yuxing Krishnamurthy, Balasubramanian Mannering, Stuart I. Kay, Thomas W. H. Thomas, Helen E. Front Immunol Immunology Diabetogenic T cells infiltrate the pancreatic islets by transmigrating across the microcapillaries residing close to, or within, the pancreatic islets. Deficiency in IFNγ signaling prevents efficient migration of T cells into the pancreatic islets, but the IFNγ-regulated molecules that mediate this are uncertain. Homing of autoreactive T cells into target tissues may require antigen specificity through presentation of cognate antigen by MHC expressed on the vascular endothelium. We investigated the hypothesis that IFNγ promotes the migration of islet antigen-specific CD4(+) T cells by upregulating MHC class II on islet endothelial cells (IEC), thereby providing an antigen-specific signal for islet infiltration. Upon IFNγ stimulation, MHC class II, which is not constitutively expressed on IEC, was induced. IFNγ-dependent upregulation of MHC class II was detected in IEC isolated from prediabetic NOD mice at the earliest stages of insulitis, before other markers of inflammation were present. Using a CD4(+) T cell-mediated adoptive transfer model of autoimmune diabetes we observed that even though diabetes does not develop in recipient mice lacking IFNγ receptors, mice with MHC class II-deficient IEC were not protected from disease. Thus, IFNγ-regulated molecules, but not MHC class II or antigen presentation by IECs is required for the early migration of antigen-specific CD4(+) T cells into the pancreatic islets. Frontiers Media S.A. 2018-11-28 /pmc/articles/PMC6282031/ /pubmed/30555479 http://dx.doi.org/10.3389/fimmu.2018.02800 Text en Copyright © 2018 Scott, Zhao, Krishnamurthy, Mannering, Kay and Thomas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Scott, Nicholas A. Zhao, Yuxing Krishnamurthy, Balasubramanian Mannering, Stuart I. Kay, Thomas W. H. Thomas, Helen E. IFNγ-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4(+) T Cell Migration |
title | IFNγ-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4(+) T Cell Migration |
title_full | IFNγ-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4(+) T Cell Migration |
title_fullStr | IFNγ-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4(+) T Cell Migration |
title_full_unstemmed | IFNγ-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4(+) T Cell Migration |
title_short | IFNγ-Induced MHC Class II Expression on Islet Endothelial Cells Is an Early Marker of Insulitis but Is Not Required for Diabetogenic CD4(+) T Cell Migration |
title_sort | ifnγ-induced mhc class ii expression on islet endothelial cells is an early marker of insulitis but is not required for diabetogenic cd4(+) t cell migration |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282031/ https://www.ncbi.nlm.nih.gov/pubmed/30555479 http://dx.doi.org/10.3389/fimmu.2018.02800 |
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