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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
Author
Bhuyan, Zaied Ahmed Department of Immunology & Parasitology, Institute of Health Biosciences, The University of Tokushima Graduate School
Asanoma, Michihito The University of Tokushima
Maekawa, Yoichi The University of Tokushima
Keywords
Notch
Rbpj
EAU (Experimental Autoimmune Uveoretinitis)
GSI (γ secretase inhibitor)
IL-22
Content Type
Thesis or Dissertation
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.
Journal Title
PLOS ONE
ISSN
19326203
Publisher
PLOS
Volume
9
Issue
2
Start Page
e89266
Published Date
2014-02-28
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/ )
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2740号
Diploma Number
甲医第1201号
Granted Date
2014-03-19
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences