mTOR signalling and metabolic regulation of T cell differentiation

Current Opinion in Immunology

Volumn 22, Issue 5, 2010, Pages 655-661

  Peter, Christian ^a   Waldmann, Herman ^a   Cobbold, Stephen P ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROTEIN; FINGOLIMOD; INTERLEUKIN 2; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN TORC1; PROTEIN TORC2; RAPAMYCIN; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG;

CD4+ T LYMPHOCYTE; CELL ENERGY; CELL FATE; CELL METABOLISM; CELL MIGRATION; CHEMOTAXIS; DRUG EFFICACY; IMMUNE RESPONSE; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTE DIFFERENTIATION; METABOLIC REGULATION; NUTRIENT AVAILABILITY; NUTRIENT UPTAKE; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY MECHANISM; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE ACTIVATION;

ANIMALS; CELL DIFFERENTIATION; CHEMOTAXIS, LEUKOCYTE; HUMANS; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; TOR SERINE-THREONINE KINASES;

EID: 78049287331     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2010.08.010     Document Type: Review

References (48)

1. Buttgereit F., Brand M.D., Muller M. ConA induced changes in energy metabolism of rat thymocytes. Biosci Rep 1992, 12:109-114.
2. Ramanathan A., Schreiber S.L. Direct control of mitochondrial function by mTOR. Proc Natl Acad Sci U S A 2009, 106:22229-22232.
3. Schieke S.M., Phillips D., McCoy J.P., Aponte A.M., Shen R.F., Balaban R.S., Finkel T. The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem 2006, 281:27643-27652.
4. Hurley R.L., Anderson K.A., Franzone J.M., Kemp B.E., Means A.R., Witters L.A. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem 2005, 280:29060-29066.
5. Woods A., Dickerson K., Heath R., Hong S.P., Momcilovic M., Johnstone S.R., Carlson M., Carling D. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2005, 2:21-33.
6. Jacobs S.R., Herman C.E., Maciver N.J., Wofford J.A., Wieman H.L., Hammen J.J., Rathmell J.C. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J Immunol 2008, 180:4476-4486.
7. Wieman H.L., Wofford J.A., Rathmell J.C. Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking. Mol Biol Cell 2007, 18:1437-1446.
8. Edinger A.L., Thompson C.B. Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Biol Cell 2002, 13:2276-2288.
9. Hay N., Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004, 18:1926-1945.
10. Laplante M. Sabatini DM: mTOR signaling at a glance. J Cell Sci 2009, 122:3589-3594.
11. Sancak Y., Peterson T.R., Shaul Y.D., Lindquist R.A., Thoreen C.C., Bar-Peled L., Sabatini D.M. The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1. Science 2008, 320:1496-1501.
12. Kim E., Goraksha-Hicks P., Li L., Neufeld T.P., Guan K.-L. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 2008, 10:935-945.
13. Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini DM Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 2010, 141:290-303.
14. Goberdhan D.C., Meredith D., Boyd C.A., Wilson C. PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids. Development 2005, 132:2365-2375.
15. Heublein S., Kazi S., Ogmundsdottir M.H., Attwood E.V., Kala S., Boyd C.A., Wilson C., Goberdhan D.C. Proton-assisted amino-acid transporters are conserved regulators of proliferation and amino-acid-dependent mTORC1 activation. Oncogene 2010, 10.1038/onc. 2010.177.
16. Reynolds B., Laynes R., Ogmundsdottir M.H., Boyd C.A., Goberdhan D.C. Amino acid transporters and nutrient-sensing mechanisms: new targets for treating insulin-linked disorders?. Biochem Soc Trans 2007, 35:1215-1217.
17. Goberdhan D.C., Ogmundsdottir M.H., Kazi S., Reynolds B., Visvalingam S.M., Wilson C., Boyd C.A. Amino acid sensing and mTOR regulation: inside or out?. Biochem Soc Trans 2009, 37:248-252.
18. Delgoffe G.M., Kole T.P., Zheng Y., Zarek P.E., Matthews K.L., Xiao B., Worley P.F., Kozma S.C., Powell J.D. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 2009, 30:832-844.
19. Keunwook Lee P.G., Srdjan Dragovic, Charles Spencer, Sebastian Joyce, Nigel Killeen, Mark A., Magnuson, Mark Boothby: Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 2010, 32:743-753.
20. Kopf H., de la Rosa G.M., Howard O.M., Chen X. Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells. Int Immunopharmacol 2007, 7:1819-1824.
21. Haxhinasto S., Mathis D., Benoist C. The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells. J Exp Med 2008, 205:565-574.
22. Sauer S., Bruno L., Hertweck A., Finlay D., Leleu M., Spivakov M., Knight Z.A., Cobb B.S., Cantrell D., O'Connor E., et al. T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc Natl Acad Sci 2008, 105:7797-7802.
23. Sarbassov D.D., Ali S.M., Sengupta S., Sheen J.H., Hsu P.P., Bagley A.F., Markhard A.L., Sabatini D.M. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006, 22:159-168.
24. Cobbold S.P., Adams E., Farquhar C.A., Nolan K.F., Howie D., Lui K.O., Fairchild P.J., Mellor A.L., Ron D., Waldmann H. Infectious tolerance via the consumption of essential amino acids and mTOR signaling. Proc Natl Acad Sci U S A 2009, 106:12055-12060.
25. Thoreen C.C., Kang S.A., Chang J.W., Liu Q., Zhang J., Gao Y., Reichling L.J., Sim T., Sabatini D.M., Gray N.S. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 2009, 284:8023-8032.
26. Harada Y., Elly C., Ying G., Paik J.H., Depinho R.A., Liu Y.C. Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells. J Exp Med 2010, 207:1381-1391.
27. Ouyang W., Beckett O., Ma Q., Paik J.H., DePinho R.A., Li MO Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells. Nat Immunol 2010, 11:618-627.
28. Merkenschlager M., von Boehmer H. PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo factors. J Exp Med 2010, 207:1347-1350.
29. Hedrick S.M. The cunning little vixen: Foxo and the cycle of life and death. Nat Immunol 2009, 10:1057-1063.
30. Francisco L.M., Salinas V.H., Brown K.E., Vanguri V.K., Freeman G.J., Kuchroo V.K., Sharpe A.H. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 2009, 206:3015-3029.
31. Basu S., Golovina T., Mikheeva T., June C.H., Riley J.L. Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin. J Immunol 2008, 180:5794-5798.
32. Battaglia M., Stabilini A., Migliavacca B., Horejs-Hoeck J., Kaupper T., Roncarolo M.G. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 2006, 177:8338-8347.
33. Battaglia M., Stabilini A., Roncarolo M.G. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 2005, 105:4743-4748.
34. reg) and effector T cells to rapamycin. PLoS One 2009, 4:e5994.
35. Strauss L., Whiteside T.L., Knights A., Bergmann C., Knuth A., Zippelius A. Selective survival of naturally occurring human CD4+CD25+Foxp3+ regulatory T cells cultured with rapamycin. J Immunol 2007, 178:320-329.
36. Wells A.D. New insights into the molecular basis of T cell anergy: anergy factors, avoidance sensors, and epigenetic imprinting. J Immunol 2009, 182:7331-7341.
37. Zheng Y., Delgoffe G.M., Meyer C.F., Chan W., Powell J.D. Anergic T cells are metabolically anergic. J Immunol 2009, 183:6095-6101.
38. Araki K., Turner A.P., Shaffer V.O., Gangappa S., Keller S.A., Bachmann M.F., Larsen C.P., Ahmed R. mTOR regulates memory CD8 T-cell differentiation. Nature 2009, 460:108-112.
39. Rao R.R., Li Q., Odunsi K., Shrikant P.A. The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity 2010, 32:67-78.
40. Pearce E.L., Walsh M.C., Cejas P.J., Harms G.M., Shen H., Wang L.S., Jones R.G., Choi Y. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 2009, 460:103-107.
41. Intlekofer A.M., Takemoto N., Wherry E.J., Longworth S.A., Northrup J.T., Palanivel V.R., Mullen A.C., Gasink C.R., Kaech S.M., Miller J.D., et al. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol 2005, 6:1236-1244.
42. Gattinoni L., Zhong X.S., Palmer D.C., Ji Y., Hinrichs C.S., Yu Z., Wrzesinski C., Boni A., Cassard L., Garvin L.M., et al. Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat Med 2009, 15:808-813.
43. Inoki K., Ouyang H., Zhu T., Lindvall C., Wang Y., Zhang X., Yang Q., Bennett C., Harada Y., Stankunas K., et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 2006, 126:955-968.
44. Araki K., Youngblood B., Ahmed R The role of mTOR in memory CD8 T-cell differentiation. Immunol Rev 2010, 235:234-243.
45. Liu G., Burns S., Huang G., Boyd K., Proia R.L., Flavell R.A., Chi H. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat Immunol 2009, 10:769-777.
46. Kunzendorf U., Ziegler E., Kabelitz D. FTY720 - the first compound of a new promising class of immunosuppressive drugs. Nephrol Dial Transplant 2004, 19:1677-1681.
47. Sinclair L.V., Finlay D., Feijoo C., Cornish G.H., Gray A., Ager A., Okkenhaug K., Hagenbeek T.J., Spits H., Cantrell D.A. Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking. Nat Immunol 2008, 9:513-521.
48. Murooka T.T., Rahbar R., Platanias L.C., Fish E.N. CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1. Blood 2008, 111:4892-4901.