Immunological Abnormality caused by MARCH I/c-MIR 2 deficiency

MARCH I/c-MIR 2 缺陷引起的免疫异常

• 批准号: 21590422
• 负责人: HOSHINO Mari
• 金额: $ 2.91万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590422/
• 关键词: E3ユビキチンリガーゼ; 樹状細胞

We have investigated the physiological function of MARCH(membrane associated RING-CH protein) family. So far, we reported that MARCH-I-deficient cDCs and B cells accumulated MHC II and B7-2 and exhibited low Ag-presenting ability for exogenous Ags. Furthermore, MHC II, but not B7-2, was required for impaired cDC function induced by loss of MARCH-I in vivo. On this study we found that conditional inhibition of MARCH-I induced natural Treg-dependent apoptosis of mature DCs due to loss of MHC II ubiquitination. Our results suggest that maturation of DCs induces their "suicide" by facilitating recognition by Tregs, which is induced by loss of pMHC II ubiquitination in the steady state.

我们研究了MARCH（膜相关RING-CH蛋白）家族的生理功能。到目前为止，我们报道了MARCH-I缺陷的cDC和B细胞积累了MHC II和B7-2，并且对外源Ag表现出较低的Ag呈递能力。此外，体内MARCH-I缺失引起的cDC功能受损需要MHC II，而不是B7-2。在这项研究中，我们发现，由于 MHC II 泛素化的丧失，条件性抑制 MARCH-I 会诱导成熟 DC 的自然 Treg 依赖性凋亡。我们的结果表明，DC 的成熟通过促进 Tregs 的识别来诱导其“自杀”，而 Tregs 是由稳态下 pMHC II 泛素化的丧失引起的。

项目成果

CD83 increases MHC II and CD86 on dendritic cells by opposing IL-10-driven MARCH1-mediated ubiquitination and degradation.

• DOI: 10.1084/jem.20092203
• 发表时间: 2011-01-17
• 期刊: The Journal of experimental medicine
• 作者: Tze LE;Horikawa K;Domaschenz H;Howard DR;Roots CM;Rigby RJ;Way DA;Ohmura-Hoshino M;Ishido S;Andoniou CE;Degli-Esposti MA;Goodnow CC
• 通讯作者: Goodnow CC

MHCクラスIIのユビキチン化は樹状細胞の維持に重要である

MHC II 类泛素化对于树突状细胞的维持很重要

• 发表时间: 2011
• 作者: 星野真理,松木洋平;水戸麻理;石川力也;後藤栄治;梶川瑞穂;八木田秀雄;石戸聡
• 通讯作者: 石戸聡

Cutting Edge: Requirement of MARCH-I-Mediated MHC II Ubiquitination for the Maintenance of Conventional Dendritic Cells

• DOI: 10.4049/jimmunol.0902178
• 发表时间: 2009-12-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Ohmura-Hoshino, Mari;Matsuki, Yohei;Ishido, Satoshi
• 通讯作者: Ishido, Satoshi

MARCH Iによる樹状細胞の制御

MARCH I 对树突状细胞的调节

• 发表时间: 2009
• 作者: 星野真理;松木洋平;水戸麻理;青木雅美;後藤栄治;石戸聡
• 通讯作者: 石戸聡