T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR

By S. Sauer, L. Bruno, Arnulf Hertweck, David K. Finlay, M. Leleu, Mikhail Spivakov, Zachary A. Knight, B. Cobb, D. Cantrell, Eric O'Connor and 3 more. Proceedings of the National Academy of Sciences of the United States of America, 2008

893 citations recorded by the source corpus.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/983ede27221397e432d176d816e13f73450bac12

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In Immunology

Citations in the corpus

Control of regulatory T cell lineage commitment and maintenance (2009, background): “Predictably, permissive chromatin modifications at Foxp3-CNS1 and the Foxp3 promoter coincide with or directly precede Foxp3 expression (Figure 2; Kim and Leonard, 2007; Mantel et al., 2006; Sauer et al., 2008; Tone et al., 2008).”
The mammalian Target of Rapamycin (mTOR) regulates T helper cell differentiation through the selective activation of mTORC1 and mTORC2 signaling (2011, background): “Rapamycin can enhance the generation of inducible T reg cell”
The PD-1 Pathway in Tolerance and Autoimmunity (2010, background): “(135) demonstrated that blockade of the PI3K ⁄ mTOR pathway and truncation of TCR signaling increased Foxp3 expression.”
Regulatory T Cells: Mechanisms of Differentiation and Function (2012, background): “Early blockade of PI3K signaling through the use of PI3K-mTOR inhibitors after 18 h of stimulation resulted in robust induction of Foxp3 (125), and sustained Akt activation inhibited the stable induction of Foxp3 in peripheral Foxp3− CD4+ T cells (126).”
Regulatory mechanisms of PD-1/PD-L1 in cancers (2024, background): “High levels of PD-L1 expression usually lead to an increase in the number of Foxp3 + Treg cells [91].”
Regulatory T Cells and Human Disease. (2020, background): “In addition, activation of the AKT signaling pathway impairs the development of natural Tregs; and inhibitors of the pathway, for example, rapamycin, can induce FoxP3 when combined with premature termination of TCR signaling (174, 175).”
The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. (2009, background): “Likewise, based on observations from PTEN null cells and pharmacologic inhibitors of PI3-kinase, Akt, and mTOR, Sauer et al. (2008) propose that the PI-3K-Akt-mTOR axis negatively regulates Foxp3 expression.”
Regulation of Immune Responses by mTOR (2011, background): “Specifically, treatment of T cells with rapamycin leads to histone H3K4me2 and 3 methylation (which promotes transcription) at the Foxp3 promoter (83).”
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells (2009, background): “In particular, Akt signaling is essential for naive T cell activation and proliferation but dispensible for T reg cell development and function (Battaglia et al., 2006; Coenen et al., 2007; Gao et al., 2007; Qu et al., 2007; Strauss et al., 2007; Haxhinasto et al., 2008; Sauer et al., 2008).”