Regulation of IL-23 expression in human monocytic cells

在感染期间，免疫系统对病毒、细菌和其他寄生虫的破坏性特性提供防御。不同类型的免疫系统细胞在诱导和维持免疫反应中扮演不同的角色。一组重要的细胞被称为单核细胞。这些细胞具有在全身迁移的能力，并向其他细胞发出信号，实际上起到了交通监督员的作用，引导其他细胞前往感染或受伤的地方。单核细胞完成这一任务的方式之一是分泌被称为细胞因子的蛋白质。白介素12是一种特别重要的细胞因子，在针对细菌或病毒感染的免疫反应中发挥着重要作用。这会激活免疫反应，清除细菌或病毒，从而从感染中恢复过来。然而，在某些情况下，单核细胞对IL-12表达的调节会因感染而中断。这可能会对感染者产生有害影响。IL-12的作用已经得到了很好的证明。然而，一种相关的细胞因子IL-23已经被新发现，它在免疫反应产生中的作用还没有很好的文献报道。已知这种细胞因子与IL-12有相似的功能，但也有明显不同的作用。了解细胞因子是如何调节的，对于疫苗设计和感染治疗至关重要。将从健康志愿者中分离出单核细胞，并研究这些细胞产生IL-23的能力。该项目旨在定义IL-23的表达是如何在分子水平上调节的。所涉及的技术将导致培训高素质的人员。预计将聘请一名研究生和一名技术员来完成这一项目。将对人类单核细胞产生IL-23的能力进行检测。这将通过检查细胞内蛋白质的激活来衡量，激酶充当信使，通知细胞产生多少细胞因子。扰乱正常的事件进程可能会扭曲给予细胞的信号，并导致免疫反应受阻。通过了解单核细胞如何调节IL-23的表达，可能会发现治疗疾病的新方法。

During infection, the immune system provides defenses against destructive properties of viruses, bacteria, and other parasites. Different types of immune system cells have different roles in the induction and maintenance of an immune response. One group of cells that is important is called monocytic cells. These cells have the ability to migrate throughout the body and give signals to other cells, in effect acting as traffic wardens to direct other cells towards sites of infection or injury. One of the ways in which the monocytes perform this is by secreting proteins termed cytokines. A particularly important cytokine, interleukin (IL)-12 plays an important role in the immune response against bacterial or viral infections. This leads to activation of an immune response resulting in clearance of the bacteria or virus and thus recovery from infection. However, in some cases, the regulation of expression of IL-12 by the monocytes becomes disrupted by infection. This may result in deleterious effects to the infected individual. The role of IL-12 has been well-documented. However a related cytokine, IL-23 has been newly discovered and its role in the generation of an immune response has not been well documented. It is known that this cytokine shares similar features with IL-12 but also has significantly different functions. Understanding of how cytokines are regulated is critical to vaccine design and treatment for infections. Monocytic cells will be isolated from healthy volunteers and the ability of these cells to produce IL-23 will be studied. The project is designed to define how IL-23 expression is regulated on a molecular level. The techniques involved will result in the training of highly qualified personnel. It is expected that one graduate student and one technician will be hired to complete this project. Human monocytics will be examined for their ability to produce IL-23. This will be measured by examining the activation of proteins inside the cell, kinases, which act as messengers to inform the cell how much cytokine to produce. Disruption of the normal course of events may distort the signals given to the cell and result in the blockade of the immune response. By understanding how monocytes regulate IL-23 expression, new ways of treating diseases may be discovered.