Molecular Mechanisms of Reduced Susceptibility of ADAP-deficient Mice to Experimental Autoimmune Encephalomyelitis (EAE)

ADAP 缺陷小鼠对实验性自身免疫性脑脊髓炎 (EAE) 易感性降低的分子机制

• 批准号: 143300340
• 负责人: Privatdozentin Dr. Annegret Reinhold
• 金额: --
• 依托单位: Institut für Molekulare und Klinische Immunologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/143300340?language=en
• 关键词: Molecular; Mechanisms; Reduced; Susceptibility; ADAP

The adhesion and degranulation-promoting adapter protein (ADAP), expressed in T cells, myeloid cells, and platelets, is known to regulate receptor-mediated inside-out signalling leading to integrin activation and adhesion. In previous studies we demonstrated that upon induction of experimental autoimmune encephalomyelitis (EAE) ADAP-deficient mice develop a significantly milder clinical course of disease and that this effect is T cell-independent. The aim of this project is to dissect the cellular and molecular mechanisms of the reduced inflammatory infiltration of the CNS and the lymphocyte accumulation in the lymph nodes of ADAP-deficient mice. For these purposes, we will analyze the impact of conditional ADAP-knockout mice on the course of EAE.

黏附和脱颗粒促进适配器蛋白(ADAP)在T细胞、髓系细胞和血小板中表达，调节受体介导的由内向外的信号转导，导致整合素的激活和黏附。在以前的研究中，我们证明了在诱导实验性自身免疫性脑脊髓炎(EAE)时，ADAP缺陷小鼠的临床病程明显较轻，并且这种影响不依赖T细胞。本研究旨在探讨ADAP基因缺陷小鼠中枢神经系统炎症浸润减少和淋巴组织中淋巴细胞聚集的细胞和分子机制。为此，我们将分析条件性ADAP基因敲除小鼠对EAE过程的影响。

项目成果

ADAP plays a pivotal role in CD4+ T cell activation but is only marginally involved in CD8+ T cell activation, differentiation, and immunity to pathogens

• DOI: 10.1189/jlb.1a0216-090rr
• 发表时间: 2017-02
• 期刊: Journal of Leukocyte Biology
• 影响因子: 5.5
• 作者: G. Parzmair;M. Gereke;Oxana Haberkorn;M. Annemann;Lisa Podlasly;S. Kliche;A. Reinhold;B. Schraven;D. Bruder

The adhesion- and degranulation-promoting adaptor protein and its role in the modulation of experimental autoimmune encephalomyelitis.

促进粘附和脱粒的衔接蛋白及其在调节实验性自身免疫性脑脊髓炎中的作用

• DOI: 10.1615/critrevimmunol.2014012162
• 发表时间: 2015
• 期刊: Critical reviews in immunology
• 影响因子: 1.3
• 作者: Engelmann S;Togni M;Kliche S;Reinhold D;Schraven B;Reinhold A
• 通讯作者: Reinhold A

A mutation within the SH2 domain of slp‐76 regulates the tissue distribution and cytokine production of iNKT cells in mice

slpâ76 SH2 结构域内的突变调节小鼠 iNKT 细胞的组织分布和细胞因子产生

• DOI: 10.1002/eji.201646331
• 发表时间: 2016
• 期刊: European Journal of Immunology
• 影响因子: 5.4
• 作者: Danzer C;Koller A;Baier J;Arnold H;Giessler C;Opoka R;Schmidt S;Willers M;Mihai S;Parsch H;Wirtz S;Daniel C;Reinhold A;Engelmann S;Kliche S;Bogdan C;Hoebe K;Mattner J
• 通讯作者: Mattner J