Interleukin- 23 (IL-23), which belongs to the IL-12 family of cytokines, has previously been described as having either redundant functions with IL-12 or promoting the differentiation of a novel CD4 T cell subset that produces IL-17. However, our data is the first to indicate that IL-23 can also negatively regulate the secretion of IFN-gamma that is induced by IL-12. Furthermore, we have also shown that IL-23 is involved in promoting IL-17 secreting CD8T cells. Our results have led us to hypothesize that IL-23 plays a novel and important role in CD8 T cell immunity against pathogens by antagonizing IL-12 induced effector functions and promoting the secretion of IL-17.
In specific Aim I, we will determine which CD8 T cell effector functions are regulated by IL-23 and whether or not IL-23 plays a role in regulating IFN-gamma production in response to infections.
Specific Aim II will identify the mechanisms and signaling pathways involved in IL-23 mediated regulation of IL-12 induced effector functions. Finally, specific Aim III will determine the role of IL- 23 in promoting the secretion of IL-17 from CD8 T cells. The information gathered from these specific aims will increase our knowledge of how IL-23 can regulate early immune responses against pathogens, by decreasing IFN-gamma production and other CD8 T cell effector functions. These studies will also delineate how IL-23 can impact the generation of adaptive immune responses by promoting IL-17 secreting CD8 T cell responses. The results of the experiments outlined within this proposal will further our knowledge of the role of cytokines, particularly IL-23, in immune responses to infectious pathogens. Understanding immune responses to disease causing microbes will enable us to more efficiently control these diseases.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F07-L (20))
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Prograis, Lawrence J
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University of North Texas
Other Domestic Higher Education
Fort Worth
United States
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Indramohan, Mohanalaxmi; Sieve, Amy N; Break, Timothy J et al. (2012) Inflammatory monocyte recruitment is regulated by interleukin-23 during systemic bacterial infection. Infect Immun 80:4099-105
Break, Timothy J; Jun, Sujung; Indramohan, Mohanalaxmi et al. (2012) Extracellular superoxide dismutase inhibits innate immune responses and clearance of an intracellular bacterial infection. J Immunol 188:3342-50
Carr, Karen D; Sieve, Amy N; Indramohan, Mohanalaxmi et al. (2011) Specific depletion reveals a novel role for neutrophil-mediated protection in the liver during Listeria monocytogenes infection. Eur J Immunol 41:2666-76
Graham, Amy C; Carr, Karen D; Sieve, Amy N et al. (2011) IL-22 production is regulated by IL-23 during Listeria monocytogenes infection but is not required for bacterial clearance or tissue protection. PLoS One 6:e17171
Sieve, Amy N; Meeks, Karen D; Lee, Suheung et al. (2010) A novel immunoregulatory function for IL-23: Inhibition of IL-12-dependent IFN-ýý production. Eur J Immunol 40:2236-47