The adaptive and innate immune systems function in an interdependent manner, with a large number of aspects of innate immune function, for example, antigen presentation, occurring in a way that directly impacts function of the adaptive immune system. To date, much of this interaction has been necessarily characterized in culture systems ex vivo, and in this regard often in atmospheric oxygen conditions. However, in vivo these cells and interactions are found in much lower oxygen conditions, and can in some cases be found in tissues with virtually no available oxygen. Our laboratory studies the role of hypoxic response in a range of tissues, including the immune system; utilizing in particular genetic mutations we have created targeting the hypoxia inducible transcription factors (HIFs). This project will focus on the role of T cell function in the context of macrophage loss of HIF function, and will contrast and compare this to changes in how T cells adapt in the absence of HIF during normal innate immune responses. The project will also characterize the metabolic changes inherent in hypoxic adaptation and show how those differ in different cell types in the immune system. As this is an extremely active area in immunology at present, the project will be adapted to the literature and current findings at the time the project itself is initiated.
1) Palazon, et al., Immunity. 2014 Oct 16;41(4):518-28. doi: 10.1016/j.immuni.2014.09.008. HIF transcription factors, inflammation, and immunity.
2) Doedens, et al., Nature Immunology 14, 1173–1182 (2013) doi:10.1038/ni.2714 Hypoxia-inducible factors enhance the effector responses of CD8+ T cells to persistent antigen