Analysis of the autoimmune phenomena that are controlled by Shp-1 in dendritic cells
Project/Area Number |
16K09887
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Collagenous pathology/Allergology
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Research Institution | Gunma University |
Principal Investigator |
KANEKO YORIAKI 群馬大学, 医学部附属病院, 講師 (00334095)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 自己免疫疾患 / シェーグレン症候群 / 樹状細胞 / Shp-1 / 自己免疫性唾液腺炎 / マクロファージ / 実験腎炎 / 自己免疫 |
Outline of Final Research Achievements |
We generated a conditional knockout mouse (Shp-1 CKO) to analyze a cytoplasmic tyrosine phosphatase Shp-1. This knockout strain specifically lacks Shp-1 in dendritic cells (DCs). Aged Shp-1 CKO secreted less salivary fluid than control mice in response to pilocarpine stimulation. Histological analysis revealed periductal foci increased in the salivary glands of Shp-1 CKO. The numbers of the cells infiltrating into the glands of Shp-1 CKO were measured by flow cytometry, and we found T and B cells increased markedly in the glands.
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Academic Significance and Societal Importance of the Research Achievements |
Shp-1 CKOは加齢に伴いIgGやC3の沈着を伴う自己免疫性の腎炎を発症し、Th1タイプの免疫応答が強いことは、すでに報告している。そして、本研究課題を通じて、老齢となったShp-1 CKOが、外分泌腺を標的とする自己免疫性の臓器障害を呈することも明らかとなった。ヒトのシェーグレン症候群(SjS)は、唾液や涙液の分泌低下など外分泌腺障害を呈する自己免疫性疾患であり、腺外症状としての自己免疫性腎炎も主要な症候である。従って、Shp-1 CKOはSjSの有用な動物モデルの1つとなる可能性が考えられた。
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Report
(4 results)
Research Products
(7 results)
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[Presentation] CD11c-specific ablation of the protein tyrosine phosphatase Shp-1 induces autoimmune sialadenitis: Is it a new model mouse for Sjoegren's syndrome?2018
Author(s)
Kinoshita Masato, Kaneko Yoriaki, Watanabe Mitsuharu, Ohishi Yuko, Shrestha Shreya, Suwa Junya, Saito Yasuyuki, Ohnishi Hiroshi, Nojima Yoshihisa, Matozaki Takashi, and Hiromura Keiju
Organizer
The 47th Annual Meeting of The Japanese Society for Immunology
Related Report
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[Presentation] 樹状細胞特異的にShp-1を欠損する遺伝子改変マウスにおける自己免疫性唾液腺炎の解析2018
Author(s)
木下雅人, 金子和光, 渡辺光治, 大石裕子, 諏訪絢也, 中里見征央, 坂入徹, 池内秀和, 前嶋明人, 野島美久, 廣村桂樹
Organizer
第62回日本リウマチ学会総会・学術集会
Related Report
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