Regulation of IL-23 expression in human monocytic cells

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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.