General control non-derepressible 2 (GCN2) in T cells controls disease progression of autoimmune neuroinflammation

Journal of Neuroimmunology

Volumn 297, Issue , 2016, Pages 117-126

  Keil, Melanie ^a   Sonner, Jana K ^a   Lanz, Tobias V ^a,b   Oezen, Iris ^a   Bunse, Theresa ^a   Bittner, Stefan ^c   Meyer, Hannah V ^d   Meuth, Sven G ^e   Wick, Wolfgang ^a,b   Platten, Michael ^a,b  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^c UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^d WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^e UNIVERSITY OF MÜNSTER   (Germany)

Author keywords

CCL2; Chemokines; Experimental autoimmune encephalomyelitis (EAE); General control non derepressible 2 (GCN2); Regulatory T cell (Treg)

Indexed keywords

CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR4; GENERAL CONTROL NON DEREPRESSIBLE 2; PROTEIN KINASE; UNCLASSIFIED DRUG; CYTOKINE; EIF2AK4 PROTEIN, MOUSE; LIPOCORTIN 5; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; MYELIN OLIGODENDROCYTE GLYCOPROTEIN (35-55); PEPTIDE FRAGMENT; PROTEIN SERINE THREONINE KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CD4+ T LYMPHOCYTE; CELL MIGRATION; CELL STRESS; CELL SURVIVAL; DISEASE COURSE; HEMATOPOIETIC CELL; LYMPHOCYTE MIGRATION; LYMPHOCYTE PROLIFERATION; LYMPHOCYTIC INFILTRATION; MOUSE; MULTIPLE SCLEROSIS; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY T LYMPHOCYTE; TUMOR IMMUNITY; ANIMAL; ASTROCYTE; BRAIN; C57BL MOUSE; CELL MOTION; CYTOLOGY; DISEASE MODEL; DRUG EFFECTS; ENDOTHELIUM CELL; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FEMALE; FLOW CYTOMETRY; GENETICS; IMMUNOLOGY; MALE; METABOLISM; NONPARAMETRIC TEST; PATHOPHYSIOLOGY; PHYSIOLOGY; TIME FACTOR; TRANSGENIC MOUSE;

ANIMALS; ANNEXIN A5; ASTROCYTES; BRAIN; CELL MOVEMENT; CYTOKINES; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; ENDOTHELIAL CELLS; FEMALE; FLOW CYTOMETRY; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; PEPTIDE FRAGMENTS; PROTEIN-SERINE-THREONINE KINASES; STATISTICS, NONPARAMETRIC; T-LYMPHOCYTES, REGULATORY; TIME FACTORS;

EID: 84973121275     PISSN: 01655728     EISSN: 18728421     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2016.05.014     Document Type: Article

References (59)

1. Balashov K.E., Rottman J.B., Weiner H.L., Hancock W.W. CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions. Proc. Natl. Acad. Sci. U. S. A. 1999, 96(12):6873-6878.
2. Bittner S., Ruck T., Schuhmann M.K., Herrmann A.M., Mohaou Maati H., Bobak N., Gobel K., Langhauser F., Stegner D., Ehling P., Borsotto M., Pape H.C., Nieswandt B., Kleinschnitz C., Heurteaux C., Galla H.J., Budde T., Wiendl H., Meuth S.G. Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS. Nat. Med. 2013, 19(9):1161-1165.
3. + T regulatory cells. J. Immunol. 2009, 183(1):145-154.
4. + regulatory T cells. Nat. Rev. Immunol. 2011, 11(2):119-130.
5. Dalla Libera D., Di Mitri D., Bergami A., Centonze D., Gasperini C., Grasso M.G., Galgani S., Martinelli V., Comi G., Avolio C., Martino G., Borsellino G., Sallusto F., Battistini L., Furlan R. T regulatory cells are markers of disease activity in multiple sclerosis patients. PLoS One 2011, 6(6).
6. Dhaeze T., Peelen E., Hombrouck A., Peeters L., Van Wijmeersch B., Lemkens N., Lemkens P., Somers V., Lucas S., Broux B., Stinissen P., Hellings N. Circulating follicular regulatory T cells are defective in multiple sclerosis. J. Immunol. 2015, 195(3):832-840.
7. Doerck S., Gobel K., Weise G., Schneider-Hohendorf T., Reinhardt M., Hauff P., Schwab N., Linker R., Maurer M., Meuth S.G., Wiendl H. Temporal pattern of ICAM-I mediated regulatory T cell recruitment to sites of inflammation in adoptive transfer model of multiple sclerosis. PLoS One 2010, 5(11).
8. + regulatory T cells in human autoimmune disease. Nat. Med. 2011, 17(6):673-675.
9. Donnelly N., Gorman A.M., Gupta S., Samali A. The eIF2alpha kinases: their structures and functions. Cell. Mol. Life Sci. 2013, 70(19):3493-3511.
10. Fallarino F., Grohmann U., You S., McGrath B.C., Cavener D.R., Vacca C., Orabona C., Bianchi R., Belladonna M.L., Volpi C., Santamaria P., Fioretti M.C., Puccetti P. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J. Immunol. 2006, 176(11):6752-6761.
11. Gadjanski I., Boretius S., Williams S.K., Lingor P., Knoferle J., Sattler M.B., Fairless R., Hochmeister S., Suhs K.W., Michaelis T., Frahm J., Storch M.K., Bahr M., Diem R. Role of n-type voltage-dependent calcium channels in autoimmune optic neuritis. Ann. Neurol. 2009, 66(1):81-93.
12. Gartner D., Hoff H., Gimsa U., Burmester G.R., Brunner-Weinzierl M.C. CD25 regulatory T cells determine secondary but not primary remission in EAE: impact on long-term disease progression. J. Neuroimmunol. 2006, 172(1-2):73-84.
13. Goverman J. Autoimmune T cell responses in the central nervous system. Nat. Rev. Immunol. 2009, 9(6):393-407.
14. Hennet T., Hagen F.K., Tabak L.A., Marth J.D. T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination. Proc. Natl. Acad. Sci. U. S. A. 1995, 92(26):12070-12074.
15. Keller T.L., Zocco D., Sundrud M.S., Hendrick M., Edenius M., Yum J., Kim Y.J., Lee H.K., Cortese J.F., Wirth D.F., Dignam J.D., Rao A., Yeo C.Y., Mazitschek R., Whitman M. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat. Chem. Biol. 2012, 8(3):311-317.
16. + regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 2002, 169(9):4712-4716.
17. Korn T., Reddy J., Gao W., Bettelli E., Awasthi A., Petersen T.R., Backstrom B.T., Sobel R.A., Wucherpfennig K.W., Strom T.B., Oukka M., Kuchroo V.K. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat. Med. 2007, 13(4):423-431.
18. Koutrolos M., Berer K., Kawakami N., Wekerle H., Krishnamoorthy G. Treg cells mediate recovery from EAE by controlling effector T cell proliferation and motility in the CNS. Acta Neuropathol. Commun. 2014, 2:163.
19. Kwidzinski E., Bunse J., Aktas O., Richter D., Mutlu L., Zipp F., Nitsch R., Bechmann I. Indolamine 2,3-dioxygenase is expressed in the CNS and down-regulates autoimmune inflammation. FASEB J. 2005, 19(10):1347-1349.
20. Maurin A.C., Jousse C., Averous J., Parry L., Bruhat A., Cherasse Y., Zeng H., Zhang Y., Harding H.P., Ron D., Fafournoux P. The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores. Cell Metab. 2005, 1(4):273-277.
21. + regulatory cells within the central nervous system. J. Immunol. 2005, 175(5):3025-3032.
22. + T lymphocytes. Proc. Natl. Acad. Sci. U. S. A. 2005, 102(33):11817-11822.
23. + T cells: analysis using depleting antibodies. J. Autoimmun. 2004, 23(1):1-7.
24. Muller A.J., DuHadaway J.B., Donover P.S., Sutanto-Ward E., Prendergast G.C. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat. Med. 2005, 11(3):312-319.
25. Muller M., Carter S.L., Hofer M.J., Manders P., Getts D.R., Getts M.T., Dreykluft A., Lu B., Gerard C., King N.J., Campbell I.L. CXCR3 signaling reduces the severity of experimental autoimmune encephalomyelitis by controlling the parenchymal distribution of effector and regulatory T cells in the central nervous system. J. Immunol. 2007, 179(5):2774-2786.
26. Muller M., Carter S., Hofer M.J., Campbell I.L. Review: the chemokine receptor CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 in neuroimmunity-a tale of conflict and conundrum. Neuropathol. Appl. Neurobiol. 2010, 36(5):368-387.
27. Munn D.H., Sharma M.D., Baban B., Harding H.P., Zhang Y., Ron D., Mellor A.L. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 2005, 22(5):633-642.
28. Nylander A., Hafler D.A. Multiple sclerosis. J. Clin. Invest. 2012, 122(4):1180-1188.
29. + regulatory T cells. J. Immunol. 2007, 179(2):958-966.
30. Opitz C.A., Wick W., Steinman L., Platten M. Tryptophan degradation in autoimmune diseases. Cell. Mol. Life Sci. 2007, 64(19-20):2542-2563.
31. Opitz C.A., Litzenburger U.M., Sahm F., Ott M., Tritschler I., Trump S., Schumacher T., Jestaedt L., Schrenk D., Weller M., Jugold M., Guillemin G.J., Miller C.L., Lutz C., Radlwimmer B., Lehmann I., von Deimling A., Wick W., Platten M. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 2011, 478(7368):197-203.
32. Orsini H., Araujo L.P., Maricato J.T., Guereschi M.G., Mariano M., Castilho B.A., Basso A.S. GCN2 kinase plays an important role triggering the remission phase of experimental autoimmune encephalomyelitis (EAE) in mice. Brain Behav. Immun. 2014, 37:177-186.
33. Perkins D.J., Barber G.N. Defects in translational regulation mediated by the alpha subunit of eukaryotic initiation factor 2 inhibit antiviral activity and facilitate the malignant transformation of human fibroblasts. Mol. Cell. Biol. 2004, 24(5):2025-2040.
34. Piedavent-Salomon M., Willing A., Engler J.B., Steinbach K., Bauer S., Eggert B., Ufer F., Kursawe N., Wehrmann S., Jager J., Reinhardt S., Friese M.A. Multiple sclerosis associated genetic variants of CD226 impair regulatory T cell function. Brain 2015, 138(Pt 11):3263-3274.
35. Platten M., Ho P.P., Youssef S., Fontoura P., Garren H., Hur E.M., Gupta R., Lee L.Y., Kidd B.A., Robinson W.H., Sobel R.A., Selley M.L., Steinman L. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 2005, 310(5749):850-855.
36. Platten M., Wick W., Van den Eynde B.J. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res. 2012, 72(21):5435-5440.
37. Platten M., von Knebel Doeberitz N., Oezen I., Wick W., Ochs K. Cancer immunotherapy by targeting IDO1/TDO and their downstream effectors. Front. Immunol. 2014, 5:673.
38. Polman C.H., O'Connor P.W., Havrdova E., Hutchinson M., Kappos L., Miller D.H., Phillips J.T., Lublin F.D., Giovannoni G., Wajgt A., Toal M., Lynn F., Panzara M.A., Sandrock A.W., Investigators A. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 2006, 354(9):899-910.
39. Prendergast G.C., Smith C., Thomas S., Mandik-Nayak L., Laury-Kleintop L., Metz R., Muller A.J. Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer. Cancer Immunol. Immunother. 2014, 63(7):721-735.
40. Ravindran R., Khan N., Nakaya H.I., Li S., Loebbermann J., Maddur M.S., Park Y., Jones D.P., Chappert P., Davoust J., Weiss D.S., Virgin H.W., Ron D., Pulendran B. Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation. Science 2014, 343(6168):313-317.
41. Ravishankar B., Liu H., Shinde R., Chaudhary K., Xiao W., Bradley J., Koritzinsky M., Madaio M.P., McGaha T.L. The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity. Proc. Natl. Acad. Sci. U. S. A. 2015, 112(34):10774-10779.
42. Ruck T., Bittner S., Epping L., Herrmann A.M., Meuth S.G. Isolation of primary murine brain microvascular endothelial cells. J. Vis. Exp. 2014, 93.
43. + precursor quinolinic acid confers resistance of gliomas to oxidative stress. Cancer Res. 2013, 73(11):3225-3234.
44. Sakurai K., Zou J.P., Tschetter J.R., Ward J.M., Shearer G.M. Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis. J. Neuroimmunol. 2002, 129(1-2):186-196.
45. Scheuner D., Patel R., Wang F., Lee K., Kumar K., Wu J., Nilsson A., Karin M., Kaufman R.J. Double-stranded RNA-dependent protein kinase phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 mediates apoptosis. J. Biol. Chem. 2006, 281(30):21458-21468.
46. Schneider-Hohendorf T., Stenner M.P., Weidenfeller C., Zozulya A.L., Simon O.J., Schwab N., Wiendl H. Regulatory T cells exhibit enhanced migratory characteristics, a feature impaired in patients with multiple sclerosis. Eur. J. Immunol. 2010, 40(12):3581-3590.
47. Sharma M.D., Baban B., Chandler P., Hou D.Y., Singh N., Yagita H., Azuma M., Blazar B.R., Mellor A.L., Munn D.H. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J. Clin. Invest. 2007, 117(9):2570-2582.
48. Steinman L. Immunology of relapse and remission in multiple sclerosis. Annu. Rev. Immunol. 2014, 32:257-281.
49. + Treg. Eur. J. Immunol. 2009, 39(4):1108-1117.
50. Sternberg N. Bacteriophage P1 site-specific recombination. III. Strand exchange during recombination at lox sites. J. Mol. Biol. 1981, 150(4):603-608.
51. Sundrud M.S., Koralov S.B., Feuerer M., Calado D.P., Kozhaya A.E., Rhule-Smith A., Lefebvre R.E., Unutmaz D., Mazitschek R., Waldner H., Whitman M., Keller T., Rao A. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science 2009, 324(5932):1334-1338.
52. Uyttenhove C., Pilotte L., Theate I., Stroobant V., Colau D., Parmentier N., Boon T., Van den Eynde B.J. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med. 2003, 9(10):1269-1274.
53. Wek R.C., Jiang H.Y., Anthony T.G. Coping with stress: eIF2 kinases and translational control. Biochem. Soc. Trans. 2006, 34(Pt 1):7-11.
54. Yamazaki T., Yang X.O., Chung Y., Fukunaga A., Nurieva R., Pappu B., Martin-Orozco N., Kang H.S., Ma L., Panopoulos A.D., Craig S., Watowich S.S., Jetten A.M., Tian Q., Dong C. CCR6 regulates the migration of inflammatory and regulatory T cells. J. Immunol. 2008, 181(12):8391-8401.
55. Yan Y., Zhang G.X., Gran B., Fallarino F., Yu S., Li H., Cullimore M.L., Rostami A., Xu H. IDO upregulates regulatory T cells via tryptophan catabolite and suppresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis. J. Immunol. 2010, 185(10):5953-5961.
56. Yednock T.A., Cannon C., Fritz L.C., Sanchez-Madrid F., Steinman L., Karin N. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992, 356(6364):63-66.
57. Yen T., Harrison C.A., Devery J.M., Leong S., Iismaa S.E., Yoshimura T., Geczy C.L. Induction of the S100 chemotactic protein, CP-10, in murine microvascular endothelial cells by proinflammatory stimuli. Blood 1997, 90(12):4812-4821.
58. + regulatory T cells. Int. Immunol. 2004, 16(2):249-256.
59. Zohar Y., Wildbaum G., Novak R., Salzman A.L., Thelen M., Alon R., Barsheshet Y., Karp C.L., Karin N. CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis. J. Clin. Invest. 2014, 124(5):2009-2022.