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Abrogation of Rbpj Attenuates Experimental Autoimmune Uveoretinitis by Inhibiting IL-22-Producing CD4(+) T Cells
Experimental autoimmune uveoretinitis (EAU) is an organ-specific T cell-mediated disease induced by immunizing mice with interphotoreceptor retinoid binding protein (IRBP). Autoaggressive CD4(+) T cells are the major pathogenic population for EAU. We investigated the contribution of Notch signaling...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938452/ https://www.ncbi.nlm.nih.gov/pubmed/24586644 http://dx.doi.org/10.1371/journal.pone.0089266 |
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author | Bhuyan, Zaied Ahmed Asanoma, Michihito Iwata, Akiko Ishifune, Chieko Maekawa, Yoichi Shimada, Mitsuo Yasutomo, Koji |
author_facet | Bhuyan, Zaied Ahmed Asanoma, Michihito Iwata, Akiko Ishifune, Chieko Maekawa, Yoichi Shimada, Mitsuo Yasutomo, Koji |
author_sort | Bhuyan, Zaied Ahmed |
collection | PubMed |
description | Experimental autoimmune uveoretinitis (EAU) is an organ-specific T cell-mediated disease induced by immunizing mice with interphotoreceptor retinoid binding protein (IRBP). Autoaggressive CD4(+) T cells are the major pathogenic population for EAU. We investigated the contribution of Notch signaling in T cells to EAU pathogenesis because Notch signaling regulates various aspects of CD4(+) T cell functions. Rbpj is required for Notch signaling, and Rbpj deficiency in T cells inhibited EAU disease severity. The amelioration of EAU in T cell-specific Rbpj-deficient mice correlated with low levels of IL-22 production from CD4(+) T cells, although IRBP-specific CD4(+) T cell proliferation and Th17 differentiation were unaffected. Administration of recombinant IL-22 during the late phase, but not the early phase, of EAU increased EAU clinical scores in T cell-specific Rbpj-deficient mice. Notch inhibition in mice immunized with IRBP with a γ-secretase inhibitor (GSI) suppressed EAU progression, even when GSI was administered as late as 13 days after IRBP immunization. Our data demonstrate that Rbpj/Notch-mediated IL-22 production in T cells has a key pathological role in the late phase of EAU, and suggest that Notch blockade might be a useful therapeutic approach for treating EAU. |
format | Online Article Text |
id | pubmed-3938452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39384522014-03-04 Abrogation of Rbpj Attenuates Experimental Autoimmune Uveoretinitis by Inhibiting IL-22-Producing CD4(+) T Cells Bhuyan, Zaied Ahmed Asanoma, Michihito Iwata, Akiko Ishifune, Chieko Maekawa, Yoichi Shimada, Mitsuo Yasutomo, Koji PLoS One Research Article Experimental autoimmune uveoretinitis (EAU) is an organ-specific T cell-mediated disease induced by immunizing mice with interphotoreceptor retinoid binding protein (IRBP). Autoaggressive CD4(+) T cells are the major pathogenic population for EAU. We investigated the contribution of Notch signaling in T cells to EAU pathogenesis because Notch signaling regulates various aspects of CD4(+) T cell functions. Rbpj is required for Notch signaling, and Rbpj deficiency in T cells inhibited EAU disease severity. The amelioration of EAU in T cell-specific Rbpj-deficient mice correlated with low levels of IL-22 production from CD4(+) T cells, although IRBP-specific CD4(+) T cell proliferation and Th17 differentiation were unaffected. Administration of recombinant IL-22 during the late phase, but not the early phase, of EAU increased EAU clinical scores in T cell-specific Rbpj-deficient mice. Notch inhibition in mice immunized with IRBP with a γ-secretase inhibitor (GSI) suppressed EAU progression, even when GSI was administered as late as 13 days after IRBP immunization. Our data demonstrate that Rbpj/Notch-mediated IL-22 production in T cells has a key pathological role in the late phase of EAU, and suggest that Notch blockade might be a useful therapeutic approach for treating EAU. Public Library of Science 2014-02-28 /pmc/articles/PMC3938452/ /pubmed/24586644 http://dx.doi.org/10.1371/journal.pone.0089266 Text en © 2014 Bhuyan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bhuyan, Zaied Ahmed Asanoma, Michihito Iwata, Akiko Ishifune, Chieko Maekawa, Yoichi Shimada, Mitsuo Yasutomo, Koji Abrogation of Rbpj Attenuates Experimental Autoimmune Uveoretinitis by Inhibiting IL-22-Producing CD4(+) T Cells |
title | Abrogation of Rbpj Attenuates Experimental Autoimmune Uveoretinitis by Inhibiting IL-22-Producing CD4(+) T Cells |
title_full | Abrogation of Rbpj Attenuates Experimental Autoimmune Uveoretinitis by Inhibiting IL-22-Producing CD4(+) T Cells |
title_fullStr | Abrogation of Rbpj Attenuates Experimental Autoimmune Uveoretinitis by Inhibiting IL-22-Producing CD4(+) T Cells |
title_full_unstemmed | Abrogation of Rbpj Attenuates Experimental Autoimmune Uveoretinitis by Inhibiting IL-22-Producing CD4(+) T Cells |
title_short | Abrogation of Rbpj Attenuates Experimental Autoimmune Uveoretinitis by Inhibiting IL-22-Producing CD4(+) T Cells |
title_sort | abrogation of rbpj attenuates experimental autoimmune uveoretinitis by inhibiting il-22-producing cd4(+) t cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938452/ https://www.ncbi.nlm.nih.gov/pubmed/24586644 http://dx.doi.org/10.1371/journal.pone.0089266 |
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