Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways

Immunity

Volumn 32, Issue 6, 2010, Pages 743-753

  Lee, Keunwook ^a   Gudapati, Prathyusha ^a   Dragovic, Srdjan ^a   Spencer, Charles ^a   Joyce, Sebastian ^a   Killeen, Nigel ^b   Magnuson, Mark A ^a   Boothby, Mark ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

CELLIMMUNO; MOLIMMUNO

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PROTEIN KINASE B; PROTEIN KINASE C; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR GATA 3; TRANSCRIPTION FACTOR T BET;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL MUTANT; CELLULAR IMMUNITY; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; LYMPHOCYTE DIFFERENTIATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; TH2 CELL;

ANIMALS; CELL DIFFERENTIATION; CELL SEPARATION; FLOW CYTOMETRY; IMMUNOBLOTTING; IN SITU NICK-END LABELING; LYMPHOCYTE ACTIVATION; MICE; PROTEIN KINASE C; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; T-LYMPHOCYTE SUBSETS; TH1 CELLS; TH2 CELLS; TRANSCRIPTION FACTORS; TRANSFECTION;

EID: 77953897189     PISSN: 10747613     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.immuni.2010.06.002     Document Type: Article

References (59)

1. Andres P.G., Howland K.C., Nirula A., Kane L.P., Barron L., Dresnek D., Sadra A., Imboden J., Weiss A., Abbas A.K. Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation. Nat. Immunol. 2004, 5:435-442.
2. Battaglia M., Stabilini A., Roncarolo M.G. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 2005, 105:4743-4748.
3. Blazar B.R., Taylor P.A., Panoskaltsis-Mortari A., Vallera D.A. Rapamycin inhibits the generation of graft-versus-host disease- and graft-versus-leukemia-causing T cells by interfering with the production of Th1 or Th1 cytotoxic cytokines. J. Immunol. 1998, 160:5355-5365.
4. Cannons J.L., Yu L.J., Hill B., Mijares L.A., Dombroski D., Nichols K.E., Antonellis A., Koretzky G.A., Gardner K., Schwartzberg P.L. SAP regulates T(H)2 differentiation and PKC-theta-mediated activation of NF-kappaB1. Immunity 2004, 21:693-706.
5. Carrière A., Cargnello M., Julien L.A., Gao H., Bonneil E., Thibault P., Roux P.P. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr. Biol. 2008, 18:1269-1277.
6. Chan T.O., Tsichlis P.N. PDK2: A complex tail in one Akt. Sci. STKE 2001, 2001:pe1.
7. Constant S.L., Bottomly K. Induction of Th1 and Th2 CD4+ T cell responses: The alternative approaches. Annu. Rev. Immunol. 1997, 15:297-322.
8. Corn R.A., Aronica M.A., Zhang F., Tong Y., Stanley S.A., Kim S.R., Stephenson L., Enerson B., McCarthy S., Mora A., Boothby M. T cell-intrinsic requirement for NF-kappa B induction in postdifferentiation IFN-gamma production and clonal expansion in a Th1 response. J. Immunol. 2003, 171:1816-1824.
9. Corn R.A., Hunter C., Liou H.C., Siebenlist U., Boothby M.R. Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation. J. Immunol. 2005, 175:2102-2110.
10. Coudronniere N., Villalba M., Englund N., Altman A. NF-kappa B activation induced by T cell receptor/CD28 costimulation is mediated by protein kinase C-theta. Proc. Natl. Acad. Sci. USA 2000, 97:3394-3399.
11. 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.
12. Dong L.Q., Liu F. PDK2: The missing piece in the receptor tyrosine kinase signaling pathway puzzle. Am. J. Physiol. Endocrinol. Metab. 2005, 289:E187-E196.
13. Facchinetti V., Ouyang W., Wei H., Soto N., Lazorchak A., Gould C., Lowry C., Newton A.C., Mao Y., Miao R.Q., et al. The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO J. 2008, 27:1932-1943.
14. Fang Y., Vilella-Bach M., Bachmann R., Flanigan A., Chen J. Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 2001, 294:1942-1945.
15. Glimcher L.H., Murphy K.M. Lineage commitment in the immune system: The T helper lymphocyte grows up. Genes Dev. 2000, 14:1693-1711.
16. Guertin D.A., Stevens D.M., Thoreen C.C., Burds A.A., Kalaany N.Y., Moffat J., Brown M., Fitzgerald K.J., Sabatini D.M. 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 2006, 11:859-871.
17. Gwinn D.M., Shackelford D.B., Egan D.F., Mihaylova M.M., Mery A., Vasquez D.S., Turk B.E., Shaw R.J. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol. Cell 2008, 30:214-226.
18. Ha S.H., Kim D.H., Kim I.S., Kim J.H., Lee M.N., Lee H.J., Kim J.H., Jang S.K., Suh P.G., Ryu S.H. PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals. Cell. Signal 2006, 18:2283-2291.
19. 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.
20. Hinton H.J., Alessi D.R., Cantrell D.A. The serine kinase phosphoinositide-dependent kinase 1 (PDK1) regulates T cell development. Nat. Immunol. 2004, 5:539-545.
21. Huang J., Lo P.F., Zal T., Gascoigne N.R., Smith B.A., Levin S.D., Grey H.M. CD28 plays a critical role in the segregation of PKC theta within the immunologic synapse. Proc. Natl. Acad. Sci. USA 2002, 99:9369-9373.
22. Ikenoue T., Inoki K., Yang Q., Zhou X., Guan K.L. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J. 2008, 27:1919-1931.
23. Inoki K., Li Y., Zhu T., Wu J., Guan K.L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 2002, 4:648-657.
24. Jacinto E., Loewith R., Schmidt A., Lin S., Rüegg M.A., Hall A., Hall M.N. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat. Cell Biol. 2004, 6:1122-1128.
25. Jacinto E., Facchinetti V., Liu D., Soto N., Wei S., Jung S.Y., Huang Q., Qin J., Su B. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 2006, 127:125-137.
26. Jiang H.R., Al Rasebi Z., Mensah-Brown E., Shahin A., Xu D., Goodyear C.S., Fukada S.Y., Liu F.T., Liew F.Y., Lukic M.L. Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis. J. Immunol. 2009, 182:1167-1173.
27. Juntilla M.M., Wofford J.A., Birnbaum M.J., Rathmell J.C., Koretzky G.A. Akt1 and Akt2 are required for alphabeta thymocyte survival and differentiation. Proc. Natl. Acad. Sci. USA 2007, 104:12105-12110.
28. Kane L.P., Weiss A. The PI-3 kinase/Akt pathway and T cell activation: Pleiotropic pathways downstream of PIP3. Immunol. Rev. 2003, 192:7-20.
29. Kane L.P., Andres P.G., Howland K.C., Abbas A.K., Weiss A. Akt provides the CD28 costimulatory signal for up-regulation of IL-2 and IFN-gamma but not TH2 cytokines. Nat. Immunol. 2001, 2:37-44.
30. Kerdiles Y., Beisner D., Tinoco R., Dejean A., Castrillon D., DePinho R., Hedrick S. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nat. Immunol. 2009, 10:176-184.
31. Konstandin M.H., Wabnitz G.H., Aksoy H., Kirchgessner H., Dengler T.J., Samstag Y. A sensitive assay for the quantification of integrin-mediated adhesiveness of human stem cells and leukocyte subpopulations in whole blood. J. Immunol. Methods 2007, 327:30-39.
32. 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.
33. Kuchroo V.K., Das M.P., Brown J.A., Ranger A.M., Zamvil S.S., Sobel R.A., Weiner H.L., Nabavi N., Glimcher L.H. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: Application to autoimmune disease therapy. Cell 1995, 80:707-718.
34. Lane P. Role of OX40 signals in coordinating CD4 T cell selection, migration, and cytokine differentiation in T helper (Th)1 and Th2 cells. J. Exp. Med. 2000, 191:201-206.
35. Laplante M., Sabatini D.M. mTOR signaling at a glance. J. Cell Sci. 2009, 122:3589-3594.
36. Letschka T., Kollmann V., Pfeifhofer-Obermair C., Lutz-Nicoladoni C., Obermair G.J., Fresser F., Leitges M., Hermann-Kleiter N., Kaminski S., Baier G. PKC-θ selectively controls the adhesion-stimulating molecule Rap1. Blood 2008, 112:4617-4627.
37. Lin X., O'Mahony A., Mu Y., Geleziunas R., Greene W.C. Protein kinase C-θ participates in NF-kappaB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase beta. Mol. Cell. Biol. 2000, 20:2933-2940.
38. Liu Y., Graham C., Parravicini V., Brown M.J., Rivera J., Shaw S. Protein kinase C θ is expressed in mast cells and is functionally involved in Fcepsilon receptor I signaling. J. Leukoc. Biol. 2001, 69:831-840.
39. Locksley R.M. Nine lives: Plasticity among T helper cell subsets. J. Exp. Med. 2009, 206:1643-1646.
40. Manning B.D., Cantley L.C. AKT/PKB signaling: Navigating downstream. Cell 2007, 129:1261-1274.
41. Marsland B.J., Soos T.J., Späth G., Littman D.R., Kopf M. Protein kinase C θ is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses. J. Exp. Med. 2004, 200:181-189.
42. McDonald P.C., Oloumi A., Mills J., Dobreva I., Maidan M., Gray V., Wederell E.D., Bally M.B., Foster L.J., Dedhar S. Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival. Cancer Res. 2008, 68:1618-1624.
43. Mora A.L., Stephenson L.M., Enerson B., Youn J., Keegan A.D., Boothby M. New programming of IL-4 receptor signal transduction in activated T cells: Stat6 induction and Th2 differentiation mediated by IL-4Ralpha lacking cytoplasmic tyrosines. J. Immunol. 2003, 171:1891-1900.
44. Ouyang W., Beckett O., Flavell R.A., Li M.O. An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance. Immunity 2009, 30:358-371.
45. Sarbassov D.D., Ali S.M., Kim D.H., Guertin D.A., Latek R.R., Erdjument-Bromage H., Tempst P., Sabatini D.M. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol. 2004, 14:1296-1302.
46. Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005, 307:1098-1101.
47. 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.
48. Scheid M.P., Marignani P.A., Woodgett J.R. Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B. Mol. Cell. Biol. 2002, 22:6247-6260.
49. Shiota C., Woo J.T., Lindner J., Shelton K.D., Magnuson M.A. Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is essential for fetal growth and viability. Dev. Cell 2006, 11:583-589.
50. 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.
51. Sun Z., Arendt C.W., Ellmeier W., Schaeffer E.M., Sunshine M.J., Gandhi L., Annes J., Petrzilka D., Kupfer A., Schwartzberg P.L., Littman D.R. PKC-θ is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes. Nature 2000, 404:402-407.
52. Tanaka Y., So T., Lebedeva S., Croft M., Altman A. Impaired IL-4 and c-Maf expression and enhanced Th1-cell development in Vav1-deficient mice. Blood 2005, 106:1286-1295.
53. Valmori D., Tosello V., Souleimanian N.E., Godefroy E., Scotto L., Wang Y., Ayyoub M. Rapamycin-mediated enrichment of T cells with regulatory activity in stimulated CD4+ T cell cultures is not due to the selective expansion of naturally occurring regulatory T cells but to the induction of regulatory functions in conventional CD4+ T cells. J. Immunol. 2006, 177:944-949.
54. Wang D., Zamorano J., Keegan A.D., Boothby M. HMG-I(Y) phosphorylation status as a nuclear target regulated through insulin receptor substrate-1 and the I4R motif of the interleukin-4 receptor. J. Biol. Chem. 1997, 272:25083-25090.
55. Wang D., Matsumoto R., You Y., Che T., Lin X.Y., Gaffen S.L., Lin X. CD3/CD28 costimulation-induced NF-kappaB activation is mediated by recruitment of protein kinase C-θ, Bcl10, and IkappaB kinase β to the immunological synapse through CARMA1. Mol. Cell. Biol. 2004, 24:164-171.
56. Wood J.E., Schneider H., Rudd C.E. TcR and TcR-CD28 engagement of protein kinase B (PKB/AKT) and glycogen synthase kinase-3 (GSK-3) operates independently of guanine nucleotide exchange factor VAV-1. J. Biol. Chem. 2006, 281:32385-32394.
57. Yang Y., Ochando J., Yopp A., Bromberg J.S., Ding Y. IL-6 plays a unique role in initiating c-Maf expression during early stage of CD4 T cell activation. J. Immunol. 2005, 174:2720-2729.
58. Zhang D.J., Wang Q., Wei J., Baimukanova G., Buchholz F., Stewart A.F., Mao X., Killeen N. Selective expression of the Cre recombinase in late-stage thymocytes using the distal promoter of the Lck gene. J. Immunol. 2005, 174:6725-6731.
59. Zhu J., Paul W.E. CD4 T cells: Fates, functions, and faults. Blood 2008, 112:1557-1569.