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提供防御。不同类型的免疫系统细胞在免疫反应的诱导和维持中起着不同的作用。一组重要的细胞被称为单核细胞。这些细胞有能力在全身范围内迁移，并向其他细胞发出信号，实际上就像交通管理员一样，引导其他细胞前往感染或受伤的部位。单核细胞实现这一功能的方法之一是分泌称为细胞因子的蛋白质。白细胞介素(IL)-12是一种特别重要的细胞因子，在对抗细菌或病毒感染的免疫反应中起着重要作用。这导致免疫反应的激活，从而清除细菌或病毒，从而从感染中恢复。然而，在某些情况下，单核细胞对IL-12表达的调节因感染而中断。这可能对受感染的个体造成有害影响。IL-12的作用已被充分证明。然而，一种相关的细胞因子IL-23是新发现的，它在产生免疫反应中的作用尚未得到很好的证明。已知该细胞因子与IL-12具有相似的特征，但也具有显著不同的功能。了解细胞因子是如何调控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单核细胞，并研究这些细胞产生IL-23的能力。该项目旨在确定在分子水平上如何调节IL-23的表达。所涉及的技术将导致训练出高素质的人员。预计将聘请一名研究生和一名技术人员完成该项目。将检查人类单核细胞产生IL-23的能力。这将通过检查细胞内蛋白质的激活来测量，激酶作为信使告知细胞产生多少细胞因子。对正常过程的破坏可能会扭曲给予细胞的信号，导致免疫反应的阻断。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.