Dendritic cell phenotype upon contact with biomaterials

描述（由申请人提供）：组合产品可将生物材料与细胞、DNA或蛋白质联合收割机组合;例如，用于疫苗的组织工程构建体和非病毒聚合物载体。组合产品的生物组分可以通过设计（例如，DNA疫苗）或通过选择（例如，组织工程构建体中的同种异体或异种细胞）。由于生物材料在此类组合产品中用作溶媒，因此，由于生物材料的佐剂作用，阐明生物材料组分在增强对生物组分的免疫应答中的作用非常重要。树突状细胞（DC）在先天免疫中的功能是识别外来病原体和“危险信号”，以启动适应性免疫应答。本研究的目的是了解生物材料接触对DC表型的影响，生物材料化学的作用及其机制。该项目的长期目标是在分子水平上设计生物材料来控制DC表型，并以这种方式控制免疫反应。具体而言，生物材料将被设计为不支持免疫应答不期望的DC成熟，如组织工程化装置，而被设计为支持免疫应答期望的DC成熟，如疫苗的非病毒递送载体。研究计划包括以下具体目标：（1）证明生物材料接触足以使DC成熟为有效的抗原呈递细胞（APC）和T细胞刺激因子，并且成熟取决于生物材料的类型和形式而受到差异调节。(2)阐明生物材料诱导DC成熟的机制，特别是天然免疫系统Toll样受体（TLR）参与的受体。(3)显示生物材料化学通过吸附的蛋白质层影响DC成熟的过程。(4)评价存在生物材料时DC的成熟程度，使其作为专职APC介导对器械相关抗原的适应性免疫应答。

DESCRIPTION (provided by applicant): Combination products can combine biomaterials with cells, DNA or proteins; e.g. tissue engineered constructs and non-viral polymeric carriers for vaccines. The biological component of combination products can be immunogenic either by design (e.g., DNA vaccine) or by selection (e.g., allogeneic or xenogeneic cells in a tissue engineered construct). Since biomaterials are used as vehicles in such combination products it is important to clarify the role of the biomaterial component in potentiating the immune responses towards the biological component due to the adjuvant effect of the biomaterial. Dendritic cells (DCs) function in innate immunity to recognize foreign pathogens and 'danger signals' to initiate an adaptive immune response. The goal of this research is to understand the effect of biomaterial contact on DC phenotype, the role of biomaterial chemistry and the mechanism involved. The long-term goal of this project is to design biomaterials on a molecular level to control DC phenotype and in this way control immune responses. Specifically, biomaterials will be designed to not support DC maturation where immune responses are undesirable, as for tissue engineered devices, while designed to support DC maturation where immune responses are desired, as for non-viral delivery vehicles for vaccines. The research plan is comprised of the following specific aims: (1) Demonstrate that biomaterial contact is sufficient for DC maturation into efficient antigen presenting cells (APCs) and T cell stimulators, and that maturation is differentially regulated depending on the type and form of the biomaterial. (2) Elucidate the mechanism of DC maturation by biomaterials, particularly the receptors involved focusing on Toll-like receptors (TLRs) of the innate immune system. (3) Show that biomaterial chemistry influences the process of DC maturation through an adsorbed protein layer. (4) Evaluate the extent of DCs maturation in the presence of biomaterials such that they act as professional APCs in mediating an adaptive immune response to device-associated antigens.