Dendritic Cell-Associated C-Type Lectins

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DC还协调和桥接先天性和适应性免疫应答。DC在对传染病的应答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作出反应。该提案将集中于不断增长的II型DC相关C型凝集素家族;该家族具有十多个DC成员，包括CD 209（DC-SIGN）、CD 207（Langerin）和Dectin-1。虽然对这个家族知之甚少，但已经清楚的是，一些DC相关的C型凝集素既与特异性内源性细胞配体结合，也与外源性感染因子结合。这些受体中的一些还可以将特定信息传递给DC。该提议的一个主要潜在假设是DC上的C型凝集素起传递病原体特异性信息的作用，这反过来对DC进行编程以指导其他细胞如何最好地响应病原体。我们已经发现了一些新的DC相关的C型凝集素（DCAL），初步设计为DCAL-1，DCAL-2，DCAL-3，DCAL-4和DCAL-5。我们建议根据一套明确的标准进一步定义这些分子及其功能。我们对DCAL-1了解最多，它只在抗原呈递细胞（APC）上表达，我们最初的努力集中在它身上。

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.