Year: 2019
Type: dissertation
Abstract: Metabolic and transcriptional pathways in T-cells are intricately woven to affect cell fate decisions and functions downstream of T-cell activation. We proposed that an understudied epigenetic and transcriptional co-regulator previously implicated in insulin signaling, growth and aerobic glycolysis, PHIP1, could provide further means to explore the crosstalk between metabolism and gene regulation in coordinating T-cell responses. We found that upon activation, PHIP1 is significantly upregulated in T-cells and demonstrates both nuclear and cytoplasmic expression, but almost exclusively localizes in the nucleus during quiescence. PHIP1-siRNA-mediated knockdowns showed that PHIP1 regulates critical genes involved in T-cell metabolism, survival and effector/memory formation, for optimal transcriptional remodeling during activation. Data trends indicate memory-specific inhibition and/or preference for effector-like responses in PHIP1-deficient T-cells, although additional in-depth studies are required to confirm this. Further investigations can potentially implicate PHIP1 as a novel candidate to reprogram T-cell metabolism and differentiation and thus enhance or temper cellular immunity.
Source: TSpace (University of Toronto)
Author: Srishti Jain
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3150244848