2011 Fiscal Year Final Research Report
Immunotherapeutic analysis using newly established murine models for Sjogren' s syndrome
| Project/Area Number |
21249090
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
HAYASHI Yoshio 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 客員教授 (00127854)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKAKI Rieko 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (40231120)
YAMADA Akiko 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (70452646)
ISHIMARU Naozumi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (60314879)
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| Project Period (FY) |
2009 – 2011
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| Keywords | シェーグレン症候群 / 自己免疫疾患 / 治療法開発 / RbAp48 / CCR7 / エストロゲン / アロマターゼ / RNA干渉 |
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| Research Abstract |
We reported that transgenic(TG) expression of RbAp48, and CCR7 knockout(KO) mice resulted in the development of autoimmune exocrinopathy resembling Sjogren' s syndrome. CD4^+ T cell-mediated autoimmune lesions were aggravated with age, in association with autoantibody productions. We obtained evidences that salivary epithelial cells can produce interferon-γand interleukin-18, which activates interferon regulatory factor-1(IRF-1), and class II transactivator(CIITA). Regulatory T(Treg) cells were significantly retained in the lymph nodes of CCR7KO mice, and failed to patrol within the exocrine organs to protect autoimmunity. The gene targeting for RbAp48 with application of in vivo siRNA administration prevented autoimmune lesions. These results indicate a novel immunocompetent role of epithelial cells, resulting in loss of local tolerance prior to developing gender-based autoimmunity.
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[Journal Article] Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development2011
Author(s)
Lei Y, Mat Ripen A, Ishimaru N, Ohigashi I, Nagasawa T, Jeker L, Bosl M, Hollander GA, Hayashi Y, de Waal Malefyt R, Nitta T, Takahama Y
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Journal Title
J. Exp. Med
Volume: 208
Pages: 383-394
Peer Reviewed
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[Journal Article] Real-time in vivo imaging of p16Ink4a reveals cross talk with p532009
Author(s)
Yamakoshi K, Takahashi A, Hirota F, Nakayama R, Ishimaru N, Kubo Y, Mann DJ, Ohmura M, Hirao A, Saya H, Arase S, Hayashi Y, Nakao K, Matsumoto M, Ohtani N, Hara E.
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Journal Title
J. Cell Biol
Volume: 186
Pages: 393-407
Peer Reviewed
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