Roles of heterogeneity of thymic medullary epithelial cells in the regulation of human immune response
| Project/Area Number |
16590286
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Sapporo Medical University School of Medicine |
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Principal Investigator |
ICHIMIYA Shingo Sapporo Medical University School of Medicine, Department of Pathology, Assistant Professor, 医学部, 講師 (30305221)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | thymic medullary epithelial cells / p53 family / T cell development / medullary scaffold / AIRE / junctional complex / 胸腺スカフォールド / タイト結合 |
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| Research Abstract |
Regulatory mechanisms of stromal cells localized in the medullary regions are mostly unknown, which are actively involved in the purging process of self-reactive T cells to avoid immune-related disorders such as allergic and autoimmune diseases. In this program, we first discovered roles of p63 and p73 of p53-related transcription factors acting as ‘a new functional marker' of medullary epithelial cells (MECs) of the human thymus and a part of them showed heterogeneous expression of p63 and p73 in their nuclei. Focusing on these findings of MECs, we also found that autoimmune regulator (AIRE), whose mutations lead to autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), had the capacity to form a complex with p63, but not p73. Interestingly, p53, p63 and p73 could solely downregulate the expression of HLA-II, whereas AIRE/p63 did not have such an activity. Together with the evidence that G228W mutation of AIRE could not bind to the AIRE-associated domain of p63, an AIRE/p63 complex in MECs might modulate the expression of HLA-II by quenching the suppressive activities of p63 to keep away from possible leakage of self-reactive CD4 T cells from the thymus. Selection events of self-reactive T cells are provided by scaffolding network of medullary stromal cells including epithelial cells and dendritic cells, which were found to be connected with junctional complex by immunohistochamical and freeze-fracture replica analyses. More interestingly, our data employing microinjection methods suggested that small molecules could be transferred form a MEC to he next ones. Thus far short peptides derived from self-antigens would be shared by MECs.
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Report
(3 results)
Research Products
(38 results)
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[Journal Article] A calcium binding protein, S100A4, mediates T cell dependent cytotoxicity as a transformation-associated antigen.2005
Author(s)
Kondo N, Ichimiya S, Tamura Y, Tonooka A, Koshiba S, Torigoe T, Kamiguchi K, Takenaga K, Sato N.
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Journal Title
Microbiol Immunol. 49
Pages: 49-56
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A^*2402 anchor substitute.2004
Author(s)
Ida K, Kawaguchi S, Sato Y, Tsukahara T, Nabeta Y, Sahara H, Ikeda H, Torigoe T, Ichimiya S, Kamiguchi K, Wada T, Nagoya S, Hiraga H, Kawai A, Ishii T, Araki N, Myoui A, Matsumoto S, Ozaki T, Yoshikawa H, Yamashita T, Sato N.
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Journal Title
J Immunol. 173
Pages: 1436-1443
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Polymorphism of Clara cell 10-kD protein gene of sarcoidosis.2004
Author(s)
Ohchi T, Shijubo N, Kawabata I, Ichimiya S, Inomata S, Yamaguchi A, Umemori Y, Itoh Y, Abe S, Hiraga Y, Sato N.
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Journal Title
Am J Respir Crit Care Med. 169
Pages: 180-186
Description
「研究成果報告書概要(欧文)」より
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