Dendritic Cell-Associated C-Type Lectins

描述(申请人提供)：树突状细胞(DC)不仅是免疫系统的关键“哨兵”，而且还协调和桥梁先天和获得性免疫反应。DC在应对传染病和慢性病过程中发挥着关键作用。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)、肿瘤坏死因子受体(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。这项建议将集中在不断增长的II型DC相关的C型凝集素家族；该家族有十几个DC成员被发现，包括CD209(DC-SIGN)，CD207(朗杰林)和Dectin-1。虽然对这个家族的了解相对较少，但已经很清楚的是，一些DC相关的C型凝集素既能与特定的内源性细胞配体结合，也能与外源性感染性物质结合。其中一些受体也可能将特定的信息传递给DC。这一建议的一个主要假设是，DC上的C型凝集素功能是传递病原体特异的信息，进而编程DC指示其他细胞如何最好地对病原体做出反应。我们发现了一些新的DC相关C型凝集素(DCAL)，初步设计了DCAL-1、DCAL-2、DCAL-3、DCAL-4和DCAL-5。我们建议基于一套定义良好的标准进一步定义这些分子及其功能。我们对DCAL-1的了解最多，它只在抗原提呈细胞(APC)上表达，我们最初的工作重点是DCAL-1。

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.