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Mechanisms of signaling via the activating immunoreceptor NKp80

通过激活免疫受体 NKp80 的信号传导机制

基本信息

批准号：
204202340
负责人：
Professor Dr. Alexander Luis Steinle
金额：
--
依托单位：
Institut für Molekulare Medizin
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2011
资助国家：
德国
起止时间：
2010-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/204202340?language=en
关键词：
Mechanisms signaling via activating immunoreceptor

项目摘要

Natural (NK) cells are part of the innate immune yystem capable of destryoing virus-infected and malignant cfells. Hence, the uage of NK cells for immuntherapy has gained considerable attention in the last years. NK cells also criticall determine the course of immune responses, e.g. y th eproductionof catokines such as Interferon-g. Further, NK-like cells have recently been implicated in the homeostasis of timmuses such as intestine or placenta. This funcitonal versatility of NK cells is reflected in a considerable number of activating receptors on NK cells. In our attempts to decipher NK cell biology by characterizing NK receptors an dtheri ligans, we identified AICL as a ligand of the NK receptor NKp80, and newly described the related receptor-ligand pair NKp65-KCAL. Both NKp80 and NKp65 are activating C-type lectin-like receptors (CTLR) encoded in the human NAtural Killer Gene Complex (NKC) adjacenly to their ligands. NKp80-AICL interaction stimulates the mutual actiavation of NK cells and monocytes, but also promotes NK-mediated cytolysis of malignant myeloid cells. Here we propose to investigate molecular mechanismsms involved in signal transduction via NKp80, since NKp80 remains one of the last activating NK receptors where signaling processes are widely unknown. Elucidating pathways of NKp80 signaling will provide new insights not only for the function of NKp80 and related receptors, but also for activation of NK cells and NK cell biology in general.

自然(NK)细胞是天然免疫系统的一部分，能够清除病毒感染的和恶性的细胞。因此，NK细胞在免疫治疗中的应用在最近几年得到了相当大的关注。自然杀伤细胞也决定免疫反应的进程，例如产生干扰素-g这样的卡托品。此外，NK样细胞最近被认为与肠道或胎盘等耳鸣的动态平衡有关。NK细胞的这种功能多样性反映在NK细胞上相当数量的激活受体上。在我们试图通过鉴定NK受体和配体来破译NK细胞生物学的过程中，我们确定AICL是NK受体NKp80的一个配体，并新描述了相关的受体-配体对NKp65-KCAL。NKp80和NKp65都激活与其配体相邻的人类自然杀伤基因复合体(NKC)中编码的C型凝集素样受体(CTLR)。NKp80-AICL相互作用刺激NK细胞和单核细胞的相互激活，但也促进NK介导的恶性髓系细胞的细胞溶解。在这里，我们建议研究通过NKp80参与信号转导的分子机制，因为NKp80仍然是最后激活的NK受体之一，其中信号转导过程广泛未知。阐明NKp80信号通路不仅将为研究NKp80及其相关受体的功能提供新的思路，而且也将为NK细胞的激活和NK细胞生物学研究提供新的思路。