The mTOR Kinase Differentially Regulates Effector and Regulatory T Cell Lineage Commitment

Abraham, 1996, Immunopharmacology of rapamycin, Annu. Rev. Immunol., 14, 483, 10.1146/annurev.immunol.14.1.483

Apostolou, 2002, Origin of regulatory T cells with known specificity for antigen, Nat. Immunol., 3, 756, 10.1038/ni816

Avruch, 2006, Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase, Oncogene, 25, 6361, 10.1038/sj.onc.1209882

Basu, 2008, Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin, J. Immunol., 180, 5794, 10.4049/jimmunol.180.9.5794

Bettelli, 2007, Th17: The third member of the effector T cell trilogy, Curr. Opin. Immunol., 19, 652, 10.1016/j.coi.2007.07.020

Chen, 2003, Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3, J. Exp. Med., 198, 1875, 10.1084/jem.20030152

Colombetti, 2006, Prolonged TCR/CD28 engagement drives IL-2-independent T cell clonal expansion through signaling mediated by the mammalian target of rapamycin, J. Immunol., 176, 2730, 10.4049/jimmunol.176.5.2730

Denning, 2007, Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses, Nat. Immunol., 8, 1086, 10.1038/ni1511

Fox, 2005, The Pim kinases control rapamycin-resistant T cell survival and activation, J. Exp. Med., 201, 259, 10.1084/jem.20042020

Gangloff, 2004, Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development, Mol. Cell. Biol., 24, 9508, 10.1128/MCB.24.21.9508-9516.2004

Guertin, 2006, Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1, Dev. Cell, 11, 859, 10.1016/j.devcel.2006.10.007

Harris, 2007, Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity, J. Immunol., 179, 4313, 10.4049/jimmunol.179.7.4313

Haxhinasto, 2008, The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells, J. Exp. Med., 205, 565, 10.1084/jem.20071477

Hay, 2004, Upstream and downstream of mTOR, Genes Dev., 18, 1926, 10.1101/gad.1212704

Ivanov, 2007, Transcriptional regulation of Th17 cell differentiation, Semin. Immunol., 19, 409, 10.1016/j.smim.2007.10.011

Kim, 2008, Regulation of interleukin-6-induced hepatic insulin resistance by mammalian target of rapamycin through the STAT3-SOCS3 pathway, J. Biol. Chem., 283, 708, 10.1074/jbc.M708568200

Kopf, 2007, Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells, Int. Immunopharmacol., 7, 1819, 10.1016/j.intimp.2007.08.027

Kretschmer, 2005, Inducing and expanding regulatory T cell populations by foreign antigen, Nat. Immunol., 6, 1219, 10.1038/ni1265

Lohr, 2006, Regulatory T cells in the periphery, Immunol. Rev., 212, 149, 10.1111/j.0105-2896.2006.00414.x

McMahon, 2002, The rapamycin-binding domain governs substrate selectivity by the mammalian target of rapamycin, Mol. Cell. Biol., 22, 7428, 10.1128/MCB.22.21.7428-7438.2002

Murphy, 2002, The lineage decisions of helper T cells, Nat. Rev. Immunol., 2, 933, 10.1038/nri954

Powell, 2006, The induction and maintenance of T cell anergy, Clin. Immunol., 120, 239, 10.1016/j.clim.2006.02.004

Powell, 2005, Low-dose radiation plus rapamycin promotes long-term bone marrow chimerism, Transplantation, 80, 1541, 10.1097/01.tp.0000185299.72295.90

Sabatini, 2006, mTOR and cancer: Insights into a complex relationship, Nat. Rev. Cancer, 6, 729, 10.1038/nrc1974

Sadlack, 1995, Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells, Eur. J. Immunol., 25, 3053, 10.1002/eji.1830251111

Safford, 2005, Egr-2 and Egr-3 are negative regulators of T cell activation, Nat. Immunol., 6, 472, 10.1038/ni1193

Sauer, 2008, T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR, Proc. Natl. Acad. Sci. USA, 105, 7797, 10.1073/pnas.0800928105

Song, 2006, Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-mediated Smad3 activation, EMBO J., 25, 58, 10.1038/sj.emboj.7600917

Tone, 2008, Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer, Nat. Immunol., 9, 194, 10.1038/ni1549

van Santen, 2004, Number of T reg cells that differentiate does not increase upon encounter of agonist ligand on thymic epithelial cells, J. Exp. Med., 200, 1221, 10.1084/jem.20041022

Weaver, 2006, Th17: An effector CD4 T cell lineage with regulatory T cell ties, Immunity, 24, 677, 10.1016/j.immuni.2006.06.002

Wiederrecht, 1995, Mechanism of action of rapamycin: New insights into the regulation of G1-phase progression in eukaryotic cells, Prog. Cell Cycle Res., 1, 53, 10.1007/978-1-4615-1809-9_5

Zeng, 2007, Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML, Blood, 109, 3509, 10.1182/blood-2006-06-030833

Zheng, 2007, A role for mammalian target of rapamycin in regulating T cell activation versus anergy, J. Immunol., 178, 2163, 10.4049/jimmunol.178.4.2163

Zhou, 2007, Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance, Proc. Natl. Acad. Sci. USA, 104, 16158, 10.1073/pnas.0702596104

Zhou, 2008, TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function, Nature, 453, 236, 10.1038/nature06878