Identification of molecules involved in differentiation and immune regulation by NK-T cells

鉴定参与 NK-T 细胞分化和免疫调节的分子

• 批准号: 14104010
• 负责人: ONOE Kazunori
• 金额: $ 71.3万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14104010/
• 关键词: NK-T cell; dendritic cell; cytokine; Thl; Th2 balance; immune regulation; atherosclerosis; arthiritis; autoimmune diseases; TLR; Th2; 自己免疫疾患; 狭心症; IL-4; IFN-γ; ネガティブフィードバック; 抗腫瘍免疫; JNK; MAPK; インターフェロン-γ; CD1d; α-GalCer; 肝炎; オステオポンチン

A new NK-T deficient strain of mice, SL/Kh, was found, where differentiation of NK-T cells was arrested at the CD40^<high> NK1.1-Ly49C/I-stage. Chemokine induced not only chemotaxis but also various functions, i.e. antigen uptake, in dendritic cells (DC), which present lipid antigens to NK-T cells (Blood 2002; 2003; Int. Immunol. 2005). DC functions to modulate Th differentiation were analyzed under different conditions (Immunology 2003a, b, c). It was found that different signal transduction systems were involved in the different cytokine productions in DC (Immunology 2006; J. Immunol. in press). Negative feed back regulation via cytokine was discovered between DC and NK-T cell interaction (Blood 2005). NK-T cells aggravated hepatitis by producing osteopontin (Immunity 2004). The osteopontin was also involved in aggravation of uveoretinitis model (J. Immunol. in press). In an arthritis model, however, NK-T cells ameliorated the clinical manifestation (Int. J. Mol. Med. 2006). Abnormal function of NK-T cells was observed in patients with Wegener's granulomatosis (Clin. Exp. Immunol. 2004). NK-T cells aggravated the atherosclerosis by producing IFN-y upon stimulation with oxidized low density lipoprotein (LDL) in murine atherosclerosis model.

发现了一种新的 NK-T 缺陷型小鼠品系 SL/Kh，其中 NK-T 细胞的分化被抑制在 CD40^<high>NK1.1-Ly49C/I 阶段。趋化因子不仅诱导趋化性，还诱导树突状细胞 (DC) 的各种功能，即抗原摄取，树突状细胞向 NK-T 细胞呈递脂质抗原 (Blood 2002；2003；Int.Immunol.2005)。在不同条件下分析了 DC 调节 Th 分化的功能（Immunology 2003a、b、c）。研究发现，不同的信号转导系统参与 DC 中不同细胞因子的产生（Immunology 2006；J.Immunol. 出版中）。在 DC 和 NK-T 细胞相互作用之间发现了通过细胞因子的负反馈调节（Blood 2005）。 NK-T 细胞通过产生骨桥蛋白而加重肝炎（Immunity 2004）。骨桥蛋白还与葡萄膜视网膜炎模型的恶化有关（J.Immunol.出版中）。然而，在关节炎模型中，NK-T 细胞改善了临床表现（Int. J. Mol. Med. 2006）。在韦格纳肉芽肿病患者中观察到 NK-T 细胞功能异常（Clin. Exp.Immunol. 2004）。在小鼠动脉粥样硬化模型中，NK-T 细胞在氧化低密度脂蛋白 (LDL) 刺激下产生 IFN-γ，从而加剧动脉粥样硬化。

项目成果

Evidence of dual function of macrophage migration inhibitory factor relevant to tumor progression and regression

巨噬细胞迁移抑制因子与肿瘤进展和消退相关的双重功能的证据

• 发表时间: 2005
• 期刊: Int. J. Mol. Med. 16
• 作者: Fukushima;T.
• 通讯作者: T.

Divergence of natural killer cell receptor and related molecule in the deciduas from sporadic miscarriage with normal chromosome karyotype

染色体核型正常的散发性流产蜕膜中自然杀伤细胞受体及相关分子的分化

• 发表时间: 2005
• 期刊: Mol. Hum. Reprod. 11
• 作者: Yamada;H.
• 通讯作者: H.

Larval antigen molecules recognized by adult immune cells of inbred xenopus laevis; Partial characterization and implication in metamorphosis

近交爪蟾成体免疫细胞识别的幼虫抗原分子；

• 发表时间: 2002
• 期刊: Dev. Growth Differ. 44
• 作者: Izutsu;Y.
• 通讯作者: Y.

Rheumatoid factors induce signaling from B-cells, thus leading to Epstein-Barr virus and B-cell activation.

类风湿因子诱导 B 细胞信号传导，从而导致 Epstein-Barr 病毒和 B 细胞激活。

• 发表时间: 2004
• 期刊: J.Virol. 78
• 作者: Shigeki Shimada;Dai Takagi;Lixin Yang
• 通讯作者: Lixin Yang

Enhanced complement sensitivity of NK-T cells in murine thymus and spleen associated with presence of serum immunoglobulin.

小鼠胸腺和脾脏中 NK-T 细胞的补体敏感性增强与血清免疫球蛋白的存在相关。

• 发表时间: 2002
• 期刊: Immunobiology 206
• 作者: Onoe;K.;Iwabuchi;K;Iwabuchi;C.;Tone;S.;Konishi.J.;Kawakami;Y.;Nishimura;M.;Onoe;K.
• 通讯作者: K.