Dendritic Cell-Associated C-Type Lectins

树突状细胞相关的 C 型凝集素

• 批准号: 7224169
• 负责人: Edward A Clark
• 金额: $ 34.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7224169
• 关键词: Antibody Formation; Antigen-Presenting Cells; Antigens; Autoimmune Diseases; B-Lymphocytes; Binding; Blood; C Type Lectin Receptors; C-Type Lectins; CD209 gene; CD4 Positive T Lymphocytes; Cell physiology; Cells; Chinese Hamster Ovary Cell; Chronic Disease; Communicable Diseases; Complex; Data; Dendritic Cells; Disease; Family; Goals; Human; Immune response; Immune system; Immunity; Individual; Infection; Infectious Agent; Inflammatory Response; Interferons; Knock-out; Knockout Mice; Lectin; Length; Ligands; Ligation; Lupus; Lymphocyte; Mucous Membrane; Mus; Numbers; Patients; Pattern recognition receptor; Play; Process; Production; Reporting; Research Personnel; Role; Salmonella typhimurium; Sentinel; Signal Transduction; Skin; Staphylococcus aureus; Structure; Testing; Toll-like receptors; Tumor Necrosis Factor Receptor; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Work; base; chemokine receptor; cytokine; dectin 1; design; human TNF protein; in vivo; insight; langerin; member; mouse model; neutralizing antibody; novel; pathogen; programs; receptor; response

DESCRIPTION (provided by applicant): Dendritic cells (DCs) not only are key 'sentinels' of the immune system, but also DCs coordinate and bridge innate and adaptive immune responses. DCs play key roles in responses to infectious diseases and in chronic disease processes. They respond to infectious agents and changes in the skin and mucosa through different families of ligands and receptors including the chemokine receptor, tumor necrosis factor (TNF), TNF receptor (TNFR), Toll-like receptor (TLR) and C-type lectin families. This proposal will focus on the growing family of type II DC-associated C-type lectins; this family has over a dozen members found of DCs including CD209 (DC-SIGN), CD207 (Langerin) and Dectin-1. While relatively little is known about this family, it is already clear that some DC-associated C-type lectins bind both to specific endogenous cellular ligands and as well as to exogenous infectious agents. Some of these receptors may also transmit specific information to DCs. A major underlying hypothesis of this proposal is that C-type lectins on DCs function to transmit pathogen-specific information, which in turn programs the DC to instruct other cells how best to respond to the pathogen. We have discovered a number of new DC-Associated C-type Lectins (DCALs) tentatively designed DCAL-1, DCAL-2, DCAL-3, DCAL-4 and DCAL-5. We propose to define these molecules further and their functions based on a set of well-defined criteria. We know the most about DCAL-1, which is expressed only on antigen presenting cells (APCs) and on which we focus our initial efforts.

描述（由申请人提供）：树突状细胞（dc）不仅是免疫系统的关键“哨兵”，而且还协调和连接先天和适应性免疫反应。dc在应对传染病和慢性疾病过程中发挥关键作用。它们通过不同的配体和受体家族，包括趋化因子受体、肿瘤坏死因子（TNF）、TNF受体（TNFR）、toll样受体（TLR）和c型凝集素家族，对感染因子和皮肤和粘膜的变化做出反应。该提案将关注不断增长的II型dc相关c型凝集素家族；这个家族有十几个成员被发现有dc，包括CD209 （DC-SIGN）、CD207 （Langerin）和Dectin-1。虽然对这个家族的了解相对较少，但已经清楚的是，一些dc相关的c型凝集素既可以与特定的内源性细胞配体结合，也可以与外源性感染因子结合。其中一些受体也可能将特定信息传递给dc。该提议的一个主要潜在假设是DC上的c型凝集素的功能是传递病原体特异性信息，这反过来又对DC进行编程，以指导其他细胞如何最好地应对病原体。我们发现了一些新的dc相关c型凝集素（dcal），初步设计为DCAL-1、DCAL-2、DCAL-3、DCAL-4和DCAL-5。我们建议在一套定义良好的标准的基础上进一步定义这些分子及其功能。我们对DCAL-1了解最多，它只在抗原提呈细胞（apc）上表达，我们最初的研究重点是它。