Immune regulation by passively acquired integral membrane proteins

预防和清除感染和癌症需要一个具有良好集成免疫反应的功能免疫系统。免疫系统使用各种机制来维持健康，了解这些免疫功能是如何调节的，对于开发有效的免疫疗法和疫苗至关重要。我们最近发现了一种免疫系统中细胞间通信的新方法。这种交流通过细胞膜和完整的膜蛋白在免疫细胞之间以及其他器官的细胞和免疫细胞之间的转移而发生。这种信息传递通过各种机制发生，但导致炎症、细胞死亡或细胞应激的条件会增加供体细胞释放膜碎片。这种细胞膜和蛋白质的转移可以赋予受体免疫细胞新的功能。我们的研究主要集中在一种免疫细胞，中性粒细胞，作为细胞膜和完整的膜蛋白的接受者。中性粒细胞是第一批被招募到炎症部位的细胞，在那里有足够的机会获得从各种细胞脱落的膜蛋白。中性粒细胞有惊人的能力从坏死和凋亡的细胞中快速获得膜蛋白，这些获得的蛋白可以改变中性粒细胞的功能。目前的研究方案将描述中性粒细胞在调节免疫反应的发展中所扮演的角色。中性粒细胞从其他细胞获得膜。中性粒细胞用来将获得的信息传递给其他免疫细胞并调节其反应的机制将被确定。了解中性粒细胞对免疫反应的调节将直接应用于改进疫苗设计，并可能揭示控制急性和慢性炎症的新策略。

The prevention and clearance of infection and cancer requires a functional immune system with a well integrated immune response. The immune system uses a wide variety of mechanisms to maintain health and understanding how these immune functions are regulated is critical for the development of effective immune therapies and vaccines. We recently identified a novel method of communication among cells in the immune system. This communication occurs through the transfer of cell membranes and integral membrane proteins between immune cells and between cells in other organs and immune cells. This transfer of information occurs by a variety of mechanisms but conditions which result in inflammation, cell death, or cellular stress increases the release of membrane fragments by donor cells. This transfer of cell membranes and proteins can confer novel functions to the recipient immune cells. Our research focuses specifically on one type of immune cell, the neutrophil, as the recipient of cell membranes and integral membrane proteins. Neutrophils are the first cells recruited to sites of inflammation where there is ample opportunity to acquire membrane proteins being shed from a variety of cells. Neutrophils have an impressive capacity to rapidly acquire membrane proteins from necrotic and apoptotic cells and these acquired proteins can alter neutrophil function. The present research proposal will characterize the roles that neutrophils, which have acquired membranes from other cells, can play in regulating the development of immune responses. The mechanisms neutrophils use to transfer acquired information to other immune cells and regulate their responses will be determined. Understanding the regulation of immune responses by neutrophils will have direct application to improving vaccine design and may reveal novel strategies for the control of acute and chronic inflammation.