Radiation-Induced Immune Dysfunction is a critical component of both acute and delayed effects of radiation exposure. To ultimately test regenerative potential of radio-mitigators in functional immune assays my current collaborative project with the Guha group has focused on the characterization of T lymphocyte activation/exhaustion markers after radiation exposure.
Exhaustion: Inhibitory signals of T-cell activation (exhaustion) is a regulatory mechanisms to maintain immune responses within a desired physiologic range and protect the host from autoimmunity. T-cell exhaustion is also an important mechanism to limit T-cell activity and preserve T-cell clones that otherwise would undergo activation-induced cell death. Importantly, negative costimulation regulates T cell differentiation.
Metabolic changes have been defined for at least some of the markers associated with an exhausted T-cell state and the involvement of metabolic switches, mediated at least in part by mitochondrial regulation are of great interest to our studies designed to test if this pathway operates after radiation exposure and if it impacts T-cell effector versus memory fate.
Radiation: Radiation exposure leads to loss of lymphocyte counts but also results in transcriptional and epigenetic changes that drive a T-cell exhausted phenotype. Our goal is to understand how radiation affects lymphocyte diversity and the integration or stabilization of costimulatory/inhibitory signals that regulate the process.
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