Analysis of in vivo functions of LMIR3/4/5

LMIR3/4/5体内功能分析

• 批准号: 20390279
• 负责人: KITAURA Jiro
• 金额: $ 11.98万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390279/
• 关键词: ノックアウトマウス; ペア型免疫レセプター; ミエロイド; 自己免疫; 自然免疫; アレルギー; 炎症; ミエロイド系細胞

In the present study, we have clarified the physiological functions of LMIR3/4/5. Co-engagement of FcεRI and LMIR3 impaired cytokine production in bone marrow-derived mast cells (BMMCs) induced by FcεRI crosslinking alone, demonstrating that LMIR3 is an inhibitory receptor. On the other hand, LMIR3 has a unique receptor to associate with FcRγ and thereby functions as an activating receptor in concert with TLR4 stimulation. We have identified T cell Ig mucin I (TIM1) by retrovirus-mediated expression cloning. Notably, LMIR5 deficiency suppressed TIM1-Fc-induced recruitment of neutrophils in the dorsal air pouch, and LMIR5 deficiency attenuated neutrophil accumulation in a model of ischemia/reperfusion injury in the kidneys in which TIM1 expression is up-regulated. In that model, LMIR5 deficiency resulted in ameliorated tubular necrosis and cast formation in the acute phase. Collectively, TIM1-LMIR5 interaction plays a physiological role in immune regulation by myeloid cells.

在本研究中，我们阐明了LMIR 3/4/5的生理功能。FcεRI和LMIR 3的共结合削弱了FcεRI单独交联诱导的骨髓源性肥大细胞（BMMC）中细胞因子的产生，表明LMIR 3是一种抑制性受体。另一方面，LMIR 3具有与FcRγ结合的独特受体，从而作为与TLR 4刺激一致的活化受体发挥作用。我们已经确定了T细胞IG粘蛋白I（TIM 1）的逆转录病毒介导的表达克隆。值得注意的是，LMIR 5缺乏抑制了背侧气囊中TIM 1-Fc诱导的中性粒细胞募集，并且LMIR 5缺乏减弱了TIM 1表达上调的肾脏缺血/再灌注损伤模型中的中性粒细胞积聚。在该模型中，LMIR 5缺乏导致急性期肾小管坏死和管型形成改善。总的来说，TIM 1-LMIR 5相互作用在骨髓细胞的免疫调节中发挥生理作用。

项目成果

Hes1 immortalizes committed progenitors and plays a role in blastic crisis of chronic myelogenous leukemia.

Hes1 使定向祖细胞永生化，并在慢性粒细胞白血病的急变中发挥作用。

• 发表时间: 2010
• 期刊: Blood. 115
• 作者: Nakahara;F.;Sakata-Yanagimoto;M.;Komeno;Y.;Kato;N.;Haraguchi;K.;Kumano;K.;Harada;Y.;Harada;H.;Kitaura;J.;Ogawa;S.;Kurokawa;M.;Kitamura;T.;Chiba;S.
• 通讯作者: S.

LMIR3ノックアウトマウスの解析;LMIR3欠損はマウス腹膜炎モデルにおける致死率を改善する

LMIR3 敲除小鼠分析；LMIR3 缺陷提高小鼠腹膜炎模型的致死率

• 发表时间: 2009
• 作者: 伊沢久未

MiR125 induces hematological malignancies in vivo

MiR125在体内诱导血液恶性肿瘤

• 发表时间: 2010
• 作者: OMasatoshi Fujihara;Daisuke Kondoh;Ryo Harasawa;Enomoto Y;Enomoto Y
• 通讯作者: Enomoto Y

AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model

• DOI: 10.1038/leu.2010.40
• 发表时间: 2010-05-01
• 期刊: LEUKEMIA
• 影响因子: 11.4
• 作者: Komeno, Y.;Kitaura, J.;Kitamura, T.
• 通讯作者: Kitamura, T.

Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia

• DOI: 10.1182/blood-2007-05-088724
• 发表时间: 2009-05-07
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Miyazaki, Kazuko;Yamasaki, Norimasa;Honda, Hiroaki
• 通讯作者: Honda, Hiroaki