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- W201647988 abstract "Abstract Peripheral naïve T-cells differentiate into regulatory, helper and other effector cells in response to a cognate antigen. The relative numbers produced of each cell type are critical for immune tolerance and affect tumor and immune-related pathologies. Specifically, the differentiation of CD25+ Foxp3+ regulatory T cells (Treg) is dictated by antigen dose with sensitivity and maintenance effects from TGF-β and IL-2. These overlapping external signals are conveyed and regulated by key intracellular players such as PI3K, PTEN, DNMT1 and Akt/mTor, eventually converging on transcription factors that control the induction of Foxp3 expression. To better understand this intricate system, we have constructed a logical model in which each molecule type is treated as an on/off variable, permitting all known intracellular players to be modeled simultaneously without adjustable parameters. Key subsystems will be modeled later at higher resolution using chemical kinetics and these models will be linked to form a comprehensive, detailed model of T cell differentiation. As a preliminary result, the logical model reproduces the experimental observation that low dose antigen favors Treg induction in the absence of exogenous TGF-β or IL-2. Construction of this model has already suggested novel experimental avenues and identified key components requiring theoretical attention. Experiments suggest that a population model with interacting and evolving phenotypes is needed to complete the picture." @default.
- W201647988 created "2016-06-24" @default.
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- W201647988 date "2010-04-01" @default.
- W201647988 modified "2023-09-25" @default.
- W201647988 title "Modeling the Role of Antigen Stimulation in Treg vs. Teff Fate Selection (36.52)" @default.
- W201647988 doi "https://doi.org/10.4049/jimmunol.184.supp.36.52" @default.
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