Phagocytosis of apoptotic cells and cross-presentation by DC

凋亡细胞的吞噬作用和 DC 的交叉呈递

• 批准号: 22790451
• 负责人: NAKAYAMA Masafumi
• 金额: $ 2.58万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790451/
• 关键词: 樹状細胞; NK細胞; MHCクラスII; 抗原提示; MHC class II; 細胞間膜輸送; 貪食; 死細胞

N atural killer (NK)cells contribute to not only innate but also adaptive immunity by interacting with dendritic cells (DCs)and T cells. All activated human NK cells express HLA-DR and can initiate MHCII-dependent CD4^+ T cell proliferation ; however, the expression of MHCII by mouse NK cells and its functional significance are controversial. In this study, we show that NK-DC interactions result in the emergence of MHCII-positive NK cells. Upon in vitro or in vivo activation, mouse conventional NK cells did not induce MHCII transcripts, but rapidly acquired MHCII protein from DCs. MHCII H2-Ab1-deficient NK cells turned I-A b-positive when adoptively transferred into wild type (WT)mice or when cultured with WT splenic DCs. NK acquisition of MHCII was mediated by intercellular membrane transfer called trogocytosis, but not upon DAP10/12 and MHCI-binding NK cell receptor signaling. MHCII-dressed NK cells concurrently acquired cost imulatory molecules such as CD80 and CD86 from DCs ; however, their expression did not reach functional levels. Therefore, MHCII-dressed NK cells inhibited DC-induced CD4^+ T cell responses rather than activated CD4^+ T cells by competitive antigen presentat ion. In a mouse model for delayed-type hypersensitivity, adoptive transfer of MHCII-dressed NK cells attenuated the footpad swelling. These results suggest that MHCII-dressed NK cells generated through NK-DC interactions regulate T cell-mediated immune r esponses.

自然杀伤（NK）细胞通过与树突状细胞（DCs）和T细胞相互作用，不仅参与先天免疫，而且参与获得性免疫。所有活化的人类NK细胞均表达HLA-DR，并可启动MHCII依赖性CD 4 ^+ T细胞增殖;然而，小鼠NK细胞的MHCII表达及其功能意义存在争议。在这项研究中，我们表明，NK-DC相互作用导致MHCII阳性NK细胞的出现。在体外或体内活化后，小鼠常规NK细胞不诱导MHCII转录物，但迅速从DC获得MHCII蛋白。当过继转移到野生型（WT）小鼠中或当与WT脾DC一起培养时，MHCII H2-Ab 1缺陷型NK细胞变成I-Ab阳性。NK获得MHCII是由称为胞间红细胞作用的细胞间膜转移介导的，但不依赖于DAP 10/12和MHCI结合NK细胞受体信号传导。MHCII修饰的NK细胞同时获得来自DC的刺激分子，如CD 80和CD 86;然而，它们的表达没有达到功能水平。因此，MHCII修饰的NK细胞抑制DC诱导的CD 4 ^+ T细胞应答，而不是通过竞争性抗原提呈激活的CD 4 ^+ T细胞。在迟发型超敏反应的小鼠模型中，过继转移MHCII修饰的NK细胞减弱了足垫肿胀。这些结果表明，通过NK-DC相互作用产生的MHCII修饰的NK细胞调节T细胞介导的免疫应答。

项目成果

Investigation of metal allergy using muse model

使用 Muse 模型研究金属过敏

• 发表时间: 2011
• 作者: Kawano M;Kumagai K;Kobayashi H;Nakayama M;Suzuki R;Ogasawara K
• 通讯作者: Ogasawara K

Timファミリー分子を介したアポトーシス細胞貪食機構

Tim家族分子介导的凋亡细胞吞噬机制

• 发表时间: 2010
• 期刊: 生物と化学(日本農芸化学会誌)
• 作者: Matsui Y;Ikesue M;Danzaki K;Morimoto J;Sato M;Tanaka S;Kojima T;Tsutsui H;and Uede T;中山勝文
• 通讯作者: 中山勝文

IFN-g production by lung NK cells is critical for the natural esistance to pulmonary metastasis of B16 melanoma in mice

肺 NK 细胞产生 IFN-g 对于小鼠 B16 黑色素瘤肺转移的自然抵抗至关重要

• 发表时间: 2011
• 期刊: J Leukoc Biol
• 作者: Takeda K;Nakayama M;Sakaki M;hayakawa Y;Imawari M;Ogasawara K;Okumura K;Smyth MJ
• 通讯作者: Smyth MJ

Investigation of metal allergy using mouse model

使用小鼠模型研究金属过敏

• 发表时间: 2011
• 作者: 川野光子;熊谷賢一;小林浩;中山勝文;鈴木隆二;小笠原康悦
• 通讯作者: 小笠原康悦

Importin β1 Protein-mediated Nuclear Localization of Death Receptor 5 (DR5) Limits DR5/Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL)-induced Cell Death of Human Tumor Cells

• DOI: 10.1074/jbc.m111.309377
• 发表时间: 2011-12-16
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kojima, Yuko;Nakayama, Masafumi;Yagita, Hideo
• 通讯作者: Yagita, Hideo