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. ? ?
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