ID | 106133 |
Title Alternative | Rbpjの欠損はCD4陽性T細胞によるIL-22産生を抑制することで実験的自己免疫性網膜ブドウ膜炎の症状を軽減させる
Abrogation of Rbpj attenuates uveoretinitis
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Author |
Bhuyan, Zaied Ahmed
Department of Immunology & Parasitology, Institute of Health Biosciences, The University of Tokushima Graduate School
Asanoma, Michihito
The University of Tokushima
Iwata, Akiko
The University of Tokushima
Ishifune, Chieko
The University of Tokushima
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Maekawa, Yoichi
The University of Tokushima
Shimada, Mitsuo
The University of Tokushima
Tokushima University Educator and Researcher Directory
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Yasutomo, Koji
The University of Tokushima
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Keywords | Notch
Rbpj
EAU (Experimental Autoimmune Uveoretinitis)
GSI (γ secretase inhibitor)
IL-22
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Content Type |
Thesis or Dissertation
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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.
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Journal Title |
PLOS ONE
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ISSN | 19326203
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Publisher | PLOS
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Volume | 9
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Issue | 2
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Start Page | e89266
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Published Date | 2014-02-28
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Remark | 内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201405131004.pdf 論文本文 : LID201405281002.pdf 本論文は, 著者Zaied Ahmed Bhuyanの学位論文として提出され, 学位審査・授与の対象となっている。 |
Rights | ©2014 Bhuyan et al. 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 credited.( https://creativecommons.org/licenses/by/4.0/ )
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第2740号
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Diploma Number | 甲医第1201号
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Granted Date | 2014-03-19
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
University Hospital
Medical Sciences
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