Pathology Presents: Molecular Regulation of Distinct Fates in T cell Immunity – To be or not to be
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Vandana Kalia, PhD
Principal Investigator, Ben Towne Center for Childhood Cancer Research
Assistant Professor, Department of Pediatrics
University of Washington
- Faculty Sponsor
Bill Mahoney, PhD
Molecular Regulation of Distinct Fates in T cell Immunity – To be or not to be
Cell-extrinsic, context-specific cues bring about heritable changes in cell fate and establish identity in biological systems. In case of T cells of the adaptive immune system, such changes are brought about by the driving TCR stimuli and ancillary cytokine signals. Our data show that heterogeneity in cytokine signaling during priming of CD8 T cell responses drives T cells towards a decision to either become long-lived memory or perish shortly. This external cue guided distinct cell-fate decision institutes genomic regulation that imprints heritable cell identity. We identified one such gene regulatory network of microRNA-17~92 that is specifically upregulated in short-lived effector cells that are decommitted from the long-lived memory lineage. This miR-17~92 fate-defining gene regulatory network engendered measurable biological outcomes such as proliferation, survival, cytokine polyfunctionality and protective capacity. My laboratory studies how external cues in T cells converge to instruct distinct cell identities and lineage fate decisions. Knowing the right signals that CD8 T cells imbibe to produce effector or long-lived memory cells will enable us to trigger specific signals to engineer designer immune outcomes in the context of cancer, autoimmunity, transplantation, infections and vaccines.