MTORC1 couples immune signals and metabolic programming to establish T reg-cell function

Nature

Volumn 499, Issue 7459, 2013, Pages 485-490

  Zeng, Hu ^a   Yang, Kai ^a   Cloer, Caryn ^a   Neale, Geoffrey ^a   Vogel, Peter ^a   Chi, Hongbo ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; CYTOKINE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; INTERLEUKIN 2; LIPID; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; MEVALONIC ACID; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3;

CATALYSIS; HOMEOSTASIS; IMMUNE SYSTEM; LIPID; METABOLISM; RODENT; SIGNALING;

ANIMAL CELL; ARTICLE; CELL FUNCTION; CELL LOSS; CELL PROLIFERATION; CHOLESTEROL METABOLISM; CONTROLLED STUDY; INFLAMMATORY DISEASE; LIPID METABOLISM; MOLECULE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAPTOR; REGULATORY T LYMPHOCYTE; STEADY STATE; T LYMPHOCYTE; UPREGULATION;

AGE OF ONSET; ANIMALS; CARRIER PROTEINS; CELL PROLIFERATION; CHOLESTEROL; CTLA-4 ANTIGEN; FORKHEAD TRANSCRIPTION FACTORS; IMMUNE TOLERANCE; INDUCIBLE T-CELL CO-STIMULATOR PROTEIN; INFLAMMATION; INTERLEUKIN-2; LIPID METABOLISM; MEVALONIC ACID; MICE; PROTEINS; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; SURVIVAL RATE; T-LYMPHOCYTES, REGULATORY;

MUS; RAPTORES;

EID: 84881192927     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature12297     Document Type: Article

References (30)

1. Chi, H. Regulation and function of mTOR signalling in T cell fate decisions. Nature Rev. Immunol. 12, 325-338 (2012).
2. Delgoffe, G. M. et al. The kinase mTOR regulates the differentiation of helperTcells through the selective activation of signaling by mTORC1 and mTORC2. Nature Immunol. 12, 295-303 (2011).
3. Lee, K. et al. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 32, 743-753 (2010).
4. Delgoffe, G. M. et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 30, 832-844 (2009).
5. + cells. J. Exp. Med. 205, 565-574 (2008). (Pubitemid 351439304)
6. Sauer, S. et al. Tcell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc. Natl Acad. Sci. USA 105, 7797-7802 (2008). (Pubitemid 351872718)
7. 1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nature Immunol. 10, 769-777 (2009).
8. reg cells. Nature Immunol. 11, 1047-1056 (2010).
9. + regulatory T cells. Blood 105, 4743-4748 (2005). (Pubitemid 40807298)
10. Laplante, M. & Sabatini, D. M. mTOR signaling in growth control and disease. Cell 149, 274-293 (2012).
11. Procaccini, C. et al. An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness. Immunity 33, 929-941 (2010).
12. Kelly, A. P. et al. Notch-induced T cell development requires phosphoinositide-dependent kinase 1. EMBO J. 26, 3441-3450 (2007). (Pubitemid 47123527)
13. Cunningham, J.T. et al. mTOR controls mitochondrial oxidative function through a YY1-PGC-1a transcriptional complex. Nature 450, 736-740 (2007). (Pubitemid 350207689)
14. + T cell memory development. Immunity 36, 68-78 (2012).
15. Gurumurthy, S. et al. The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature 468, 659-663 (2010).
16. + naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol. 10, 1969-1980 (1998). (Pubitemid 28566059)
17. + regulatory T cells in the steady state. J. Exp. Med. 198, 737-746 (2003). (Pubitemid 37087773)
18. + suppressor T cells in vivo. Nature Immunol. 3, 33-41 (2002). (Pubitemid 34065615)
19. + T cell suppressor function. J. Immunol. 172, 6519-6523 (2004). (Pubitemid 38669083)
20. + T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion. J. Exp. Med. 199, 1479-1489 (2004). (Pubitemid 38780403)
21. + regulatory T cell function. Science 322, 271-275 (2008).
22. Rubtsov, Y. P. et al. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28, 546-558 (2008).
23. Kanangat, S. et al. Disease in the scurfy (sf) mouse is associated with overexpression of cytokine genes. Eur. J. Immunol. 26, 161-165 (1996). (Pubitemid 26028428)
24. Chaudhry, A. et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity 34, 566-578 (2011).
25. Josefowicz, S. Z., Lu, L. F. & Rudensky, A. Y. Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 30, 531-564 (2012).
26. reg cell function. Nature 491, 554-559 (2012).
27. Wang, R.& Green, D. R. Metabolic checkpointsin activated T cells. Nature Immunol. 13, 907-915 (2012).
28. + T cells. Blood 119, 5155-5163 (2012).
29. Corse, E. & Allison, J. P. Cutting edge: CTLA-4 on effector T cells inhibits in trans. J. Immunol. 189, 1123-1127 (2012).
30. Sadlack, B. et al. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75, 253-261 (1993). (Pubitemid 23320289)