| Project/Area Number |
20390282
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Juntendo University |
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Principal Investigator |
OKUMURA Ko Juntendo University, 大学院・医学研究科, 特任教授 (50009700)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Hiroyasu 順天堂大学, 大学院・医学研究科, 准教授 (70276476)
AKIBA Hisaya 順天堂大学, 大学院・医学研究科, 准教授 (60338316)
USHIO Hiroko 順天堂大学, 大学院・医学研究科, 准教授 (30317391)
中山 勝文 順天堂大学, 医学部, 助教 (20453582)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | TIMファミリー / マスト細胞 / アレルギー / アポトーシス / T cell immunoglobulin and mucin domain (TIM)ファミリー / TIM-2 / B細胞 / T細胞 / Th1細胞 / Th2細胞 / Th17細胞 / コラーゲン誘発性関節炎 / オートファジー / インターフェロン / Liht chain(LC)3 / ノックアウトマウス / 脱顆粒 / IgE / CD63 / Tim-3 / 樹状細胞 / 貪食 / クロスプレゼンテーション |
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| Research Abstract |
Members of the T-cell immunoglobulin mucin (Tim) family control a variety of immune responses including Th1 and Th2 differentiation of T cells. We found that TIM-3 was expressed on C8+ dendritic cells (DC) and TIM-3 was crucial for clearance of apoptotic cells by phagocytes. Moreover, TIM-3-dependent phagocytosis of apoptotic cells was crucial for cross-presentation of dying cell-associated antigens. On the other hand, TIM-2 was found to be expressed on B cells and induced positive signals into B cells. Therefore, administration of agonistic anti-TIM-2 antibody significantly exacerbated type II collagen-induced arthritis. We next investigated a role for autophagy in the development and function of mast cells. We found that conversion of type I to type II light chain (LC3)-II, a hallmark of autophagy, was constitutively induced in mast cells under full nutrient conditions, and LC3-II localized in secretory granules of mast cells. Although deletion of Atg7 did not impair the development of BMMCs, Atg7(-/-) BMMCs showed severe impairment of degranulation, but not cytokine production upon antigen stimulation.
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