Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells

Journal of Experimental Medicine

Volumn 208, Issue 11, 2011, Pages 2291-2303

  Ghoreschi, Kamran ^a   Brück, Jürgen ^a   Kellerer, Christina ^a   Deng, Caishu ^c,d   Peng, Haiyan ^e   Rothfuss, Oliver ^b   Hussain, Rehana Z ^c,d   Gocke, Anne R ^c,d   Respa, Annedore ^a   Glocova, Ivana ^a   Valtcheva, Nadejda ^b   Alexander, Eva ^b   Feil, Susanne ^b   Feil, Robert ^b   Schulze Osthoff, Klaus ^b   Rupec, Rudolf A ^f   Lovett Racke, Amy E ^c,d,e   Dringen, Ralf ^g   Racke, Michael K ^c,d,e   Röcken, Martin ^a  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^b UNIVERSITY OF TÜBINGEN   (Germany)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^d UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^e THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

^f LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^g UNIVERSITY OF BREMEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

DIMETHYLFUMARATE; FAG 201; FUMARIC ACID; GLUTATHIONE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 12P35; INTERLEUKIN 23; INTERLEUKIN 23P19; INTERLEUKIN 4; MONOMETHYLFUMARATE; PLACEBO; STAT1 PROTEIN; TRANSCRIPTION FACTOR AP 1; UNCLASSIFIED DRUG;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DENDRITIC CELL; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; MULTIPLE SCLEROSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PSORIASIS; TH1 CELL; TH17 CELL; TH2 CELL;

ANIMALS; CELL DIFFERENTIATION; DENDRITIC CELLS; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; FUMARATES; HEME OXYGENASE-1; HUMANS; INTERLEUKIN-12; INTERLEUKIN-23; MACROPHAGES; MICE; MULTIPLE SCLEROSIS; NIH 3T3 CELLS; PROMOTER REGIONS, GENETIC; PSORIASIS; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; TRANSCRIPTION FACTOR RELA;

EID: 80055106751     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20100977     Document Type: Article

References (57)

1. Altmeyer, P.J., U. Matthes, F. Pawlak, K. Hoffmann, P.J. Frosch, P. Ruppert, S.W. Wassilew, T. Horn, H.W. Kreysel, G. Lutz, et al. 1994. Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients. J. Am. Acad. Dermatol. 30:977-981. http://dx.doi.org/10.1016/S0190-9622(94)70121-0.
2. Arbiser, J.L. 2011. Fumarate esters as angiogenesis inhibitors: key to action in psoriasis? J. Invest. Dermatol. 131:1189-1191. http://dx.doi.org/10.1038/jid.2011.45.
3. Axtell, R.C., B.A. de Jong, K. Boniface, L.F. van der Voort, R. Bhat, P. De Sarno, R. Naves, M. Han, F. Zhong, J.G. Castellanos, et al. 2010. T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat. Med. 16: 406-412. http://dx.doi.org/10.1038/nm.2110.
4. Becher, B., B.G. Durell, and R.J. Noelle. 2002. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J. Clin. Invest. 110:493-497.
5. Bettelli, E., B. Sullivan, S.J. Szabo, R.A. Sobel, L.H. Glimcher, and V.K. Kuchroo. 2004. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J. Exp. Med. 200:79-87. http://dx.doi.org/10.1084/jem.20031819.
6. Biedermann, T., R. Mailhammer, A. Mai, C. Sander, A. Ogilvie, F. Brombacher, K. Maier, A.D. Levine, and M. Röcken. 2001a. Reversal of established delayed type hypersensitivity reactions following therapy with IL-4 or antigen-specific Th2 cells. Eur. J. Immunol. 31:1582-1591. http://dx.doi.org/10.1002/1521-4141(200105)31:5<1582::AID-IMMU1582>3.0.CO;2-M.
7. Biedermann, T., S. Zimmermann, H. Himmelrich, A. Gumy, O. Egeter, A.K. Sakrauski, I. Seegmüller, H. Voigt, P. Launois, A.D. Levine, et al. 2001b. IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice. Nat. Immunol. 2:1054-1060. http://dx.doi.org/10.1038/ni725.
8. Burton, P.R., D.G. Clayton, L.R. Cardon, N. Craddock, P. Deloukas, A. Duncanson, D.P. Kwiatkowski, M.I. McCarthy, W.H. Ouwehand, N.J. Samani, et al. 2007. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat. Genet. 39:1329-1337. http://dx.doi.org/10.1038/ng.2007.17.
9. Carmody, R.J., Q. Ruan, H.-C. Liou, and Y.H. Chen. 2007. Essential roles of c-Rel in TLR-induced IL-23 p19 gene expression in dendritic cells. J. Immunol. 178:186-191.
10. Chora, A.A., P. Fontoura, A. Cunha, T.F. Pais, S. Cardoso, P.P. Ho, L.Y. Lee, R.A. Sobel, L. Steinman, and M.P. Soares. 2007. Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation. J. Clin. Invest. 117:438-447. http://dx.doi.org/10.1172/JCI28844.
11. de Jong, R., A.C. Bezemer, T.P. Zomerdijk, T. van de Pouw-Kraan, T.H. Ottenhoff, and P.H. Nibbering. 1996. Selective stimulation of T helper 2 cytokine responses by the anti-psoriasis agent monomethylfumarate. Eur. J. Immunol. 26:2067-2074. http://dx.doi.org/10.1002/eji.1830260916.
12. Dringen, R., and B. Hamprecht. 1996. Glutathione content as an indicator for the presence of metabolic pathways of amino acids in astroglial cultures. J. Neurochem. 67:1375-1382. http://dx.doi.org/10.1046/j.1471-4159.1996.67041375.x.
13. Dudziak, D., A.O. Kamphorst, G.F. Heidkamp, V.R. Buchholz, C. Trumpfheller, S. Yamazaki, C. Cheong, K. Liu, H.W. Lee, C.G. Park, et al. 2007. Differential antigen processing by dendritic cell subsets in vivo. Science. 315:107-111. http://dx.doi.org/10.1126/science.1136080.
14. Durchdewald, M., T.A. Beyer, D.A. Johnson, J.A. Johnson, S. Werner, and U. auf dem Keller. 2007. Electrophilic chemicals but not UV irradiation or reactive oxygen species activate Nrf2 in keratinocytes in vitro and in vivo. J. Invest. Dermatol. 127:646-653. http://dx.doi.org/10.1038/sj.jid.5700585.
15. Frohman, E.M., M.K. Racke, and C.S. Raine. 2006. Multiple sclerosis- the plaque and its pathogenesis. N. Engl. J. Med. 354:942-955. http://dx.doi.org/10.1056/NEJMra052130.
16. Gautier, G., M. Humbert, F. Deauvieau, M. Scuiller, J. Hiscott, E.E. Bates, G. Trinchieri, C. Caux, and P. Garrone. 2005. A type I interferon autocrine-paracrine loop is involved in Toll-like receptor-induced interleukin-12p70 secretion by dendritic cells. J. Exp. Med. 201:1435-1446. http://dx.doi.org/10.1084/jem.20041964.
17. Ghashghaeinia, M., D. Bobbala, T. Wieder, S. Koka, J. Brück, B. Fehrenbacher, M. Röcken, M. Schaller, F. Lang, and K. Ghoreschi. 2010. Targeting glutathione by dimethylfumarate protects against experimental malaria by enhancing erythrocyte cell membrane scrambling. Am. J. Physiol. Cell Physiol. 299:C791-C804. http://dx.doi.org/10.1152/ajpcell.00014.2010.
18. Ghoreschi, K., U. Mrowietz, and M. Röcken. 2003a. A molecule solves psoriasis? Systemic therapies for psoriasis inducing interleukin 4 and Th2 responses. J. Mol. Med. 81:471-480. http://dx.doi.org/10.1007/s00109-003-0460-9.
19. Ghoreschi, K., P. Thomas, S. Breit, M. Dugas, R. Mailhammer, W. van Eden, R. van der Zee, T. Biedermann, J. Prinz, M. Mack, et al. 2003b. Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat. Med. 9:40-46. http://dx.doi.org/10.1038/nm804.
20. Gilliland, F.D., Y.F. Li, A. Saxon, and D. Diaz-Sanchez. 2004. Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study. Lancet. 363:119-125. http://dx.doi.org/10.1016/S0140-6736(03)15262-2.
21. Graupner, V., E. Alexander, T. Overkamp, O. Rothfuss, V. De Laurenzi, B.F. Gillissen, P.T. Daniel, K. Schulze-Osthoff, and F. Essmann. 2011. Differential regulation of the proapoptotic multidomain protein Bak by p53 and p73 at the promoter level. Cell Death Differ. 18:1130-1139. http://dx.doi.org/10.1038/cdd.2010.179.
22. Hegazi, R.A., K.N. Rao, A. Mayle, A.R. Sepulveda, L.E. Otterbein, and S.E. Plevy. 2005. Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway. J. Exp. Med. 202: 1703-1713. http://dx.doi.org/10.1084/jem.20051047 Jeannin, P., Y. Delneste, S. Lecoanet-Henchoz, J.F. Gauchat, P. Life,.
23. D. Holmes, and J.Y. Bonnefoy. 1995. Thiols decrease human interleukin (IL) 4 production and IL-4-induced immunoglobulin synthesis. J. Exp. Med. 182:1785-1792. http://dx.doi.org/10.1084/jem.182.6.1785.
24. Kappos, L., R. Gold, D.H. Miller, D.G. Macmanus, E. Havrdova, V. Limmroth, C.H. Polman, K. Schmierer, T.A. Yousry, M. Yang, et al. 2008. Efficacy and safety of oral fumarate in patients with relapsingremitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet. 372:1463-1472. http://dx.doi.org/10.1016/S0140-6736(08)61619-0.
25. Kapsenberg, M.L. 2003. Dendritic-cell control of pathogen-driven T-cell polarization. Nat. Rev. Immunol. 3:984-993. http://dx.doi.org/10.1038/nri1246.
26. Keyse, S.M., and R.M. Tyrrell. 1989. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc. Natl. Acad. Sci. USA. 86:99-103. http://dx.doi.org/10.1073/pnas.86.1.99.
27. Kim, H.S., I.H. Cho, J.E. Kim, Y.J. Shin, J.H. Jeon, Y. Kim, Y.M. Yang, K.H. Lee, J.W. Lee, W.J. Lee, et al. 2008. Ethyl pyruvate has an antiinflammatory effect by inhibiting ROS-dependent STAT signaling in activated microglia. Free Radic. Biol. Med. 45:950-963. http://dx.doi.org/10.1016/j.freeradbiomed.2008.06.009.
28. Kneilling, M., R. Mailhammer, L. Hültner, T. Schönberger, K. Fuchs, M. Schaller, D. Bukala, S. Massberg, C.A. Sander, H. Braumüller, et al. 2009. Direct crosstalk between mast cell-TNF and TNFR1-expressing endothelia mediates local tissue inflammation. Blood. 114:1696-1706. http://dx.doi.org/10.1182/blood-2008-11-187682.
29. Kortylewski, M., H. Xin, M. Kujawski, H. Lee, Y. Liu, T. Harris, C. Drake, D. Pardoll, and H. Yu. 2009. Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell. 15:114-123. http://dx.doi.org/10.1016/j.ccr.2008.12.018.
30. Krueger, G.G., R.G. Langley, C. Leonardi, N. Yeilding, C. Guzzo, Y. Wang, L.T. Dooley, and M. Lebwohl. 2007. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N. Engl. J. Med. 356:580-592. http://dx.doi.org/10.1056/NEJMoa062382.
31. Lehmann, J.C., J.J. Listopad, C.U. Rentzsch, F.H. Igney, A. von Bonin, H.H. Hennekes, K. Asadullah, and W.D. Docke. 2007. Dimethylfumarate induces immunosuppression via glutathione depletion and subsequent induction of heme oxygenase 1. J. Invest. Dermatol. 127:835-845. http://dx.doi.org/10.1038/sj.jid.5700686.
32. Lin, Q., S. Weis, G. Yang, Y.-H. Weng, R. Helston, K. Rish, A. Smith, J. Bordner, T. Polte, F. Gaunitz, and P.A. Dennery. 2007. Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress. J. Biol. Chem. 282:20621-20633. http:// dx.doi.org/10.1074/jbc.M607954200.
33. Linker, R.A., D.H. Lee, S. Ryan, A.M. van Dam, R. Conrad, P. Bista, W. Zeng, X. Hronowsky, A. Buko, S. Chollate, et al. 2011. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 134:678-692. http://dx.doi.org/10.1093/brain/awq386.
34. Litjens, N.H., P.H. Nibbering, A.J. Barrois, T.P. Zomerdijk, A.C. Van Den Oudenrijn, K.C. Noz, M. Rademaker, P.H. Van De Meide, J.T. Van Dissel, and B. Thio. 2003. Beneficial effects of fumarate therapy in psoriasis vulgaris patients coincide with downregulation of type 1 cytokines. Br. J. Dermatol. 148:444-451. http://dx.doi.org/10.1046/j.1365-2133.2003.05153.x.
35. Litjens, N.H., M. Rademaker, B. Ravensbergen, D. Rea, M.J. van der Plas, B. Thio, A. Walding, J.T. van Dissel, and P.H. Nibbering. 2004. Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses. Eur. J. Immunol. 34:565-575. http://dx.doi.org/10.1002/eji.200324174.
36. Liu, J., X. Guan, T. Tamura, K. Ozato, and X. Ma. 2004. Synergistic activation of interleukin-12 p35 gene transcription by interferon regulatory factor-1 and interferon consensus sequence-binding protein. J. Biol. Chem. 279:55609-55617. http://dx.doi.org/10.1074/jbc.M406565200.
37. Liu, W., X. Ouyang, J. Yang, J. Liu, Q. Li, Y. Gu, M. Fukata, T. Lin, J.C. He, M. Abreu, et al. 2009. AP-1 activated by toll-like receptors regulates expression of IL-23 p19. J. Biol. Chem. 284:24006-24016. http://dx.doi.org/10.1074/jbc.M109.025528.
38. Loewe, R., W. Holnthoner, M. Gröger, M. Pillinger, F. Gruber, D. Mechtcheriakova, E. Hofer, K. Wolff, and P. Petzelbauer. 2002. Dimethylfumarate inhibits TNF-induced nuclear entry of NF-kappa B/p65 in human endothelial cells. J. Immunol. 168:4781-4787.
39. Lutz, M.B., N. Kukutsch, A.L. Ogilvie, S. Rössner, F. Koch, N. Romani, and G. Schuler. 1999. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J. Immunol. Methods. 223:77-92. http://dx.doi.org/10.1016/S0022-1759(98)00204-X.
40. Mazzoni, A., and D.M. Segal. 2004. Controlling the Toll road to dendritic cell polarization. J. Leukoc. Biol. 75:721-730. http://dx.doi.org/10.1189/jlb.1003482.
41. Menges, M., S. Rössner, C. Voigtländer, H. Schindler, N.A. Kukutsch, C. Bogdan, K. Erb, G. Schuler, and M.B. Lutz. 2002. Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity. J. Exp. Med. 195:15-21. http://dx.doi.org/10.1084/jem.20011341.
42. Mise-Omata, S., E. Kuroda, J. Niikura, U. Yamashita, Y. Obata, and T.S. Doi. 2007. A proximal kappaB site in the IL-23 p19 promoter is responsible for RelA- and c-Rel-dependent transcription. J. Immunol. 179:6596-6603.
43. Mrowietz, U., and K. Asadullah. 2005. Dimethylfumarate for psoriasis: more than a dietary curiosity. Trends Mol. Med. 11:43-48. http://dx.doi.org/10.1016/j.molmed.2004.11.003.
44. Nair, R.P., K.C. Duffin, C. Helms, J. Ding, P.E. Stuart, D. Goldgar, J.E. Gudjonsson, Y. Li, T. Tejasvi, B.J. Feng, et al. 2009. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat. Genet. 41:199-204. http://dx.doi.org/10.1038/ng.311.
45. Nakahira, K., H.P. Kim, X.H. Geng, A. Nakao, X. Wang, N. Murase, P.F. Drain, X. Wang, M. Sasidhar, E.G. Nabel, et al. 2006. Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROSinduced trafficking of TLRs to lipid rafts. J. Exp. Med. 203:2377-2389. http://dx.doi.org/10.1084/jem.20060845.
46. Napolitani, G., A. Rinaldi, F. Bertoni, F. Sallusto, and A. Lanzavecchia. 2005. Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat. Immunol. 6:769-776. http://dx.doi.org/10.1038/ni1223.
47. Nestle, F.O., D.H. Kaplan, and J. Barker. 2009. Psoriasis. N. Engl. J. Med. 361:496-509. http://dx.doi.org/10.1056/NEJMra0804595.
48. Peterson, J.D., L.A. Herzenberg, K. Vasquez, and C. Waltenbaugh. 1998. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc. Natl. Acad. Sci. USA. 95:3071-3076. http://dx.doi.org/10.1073/pnas.95.6.3071.
49. Polman, C.H., P.W. O'Connor, E. Havrdova, M. Hutchinson, L. Kappos, D.H. Miller, J.T. Phillips, F.D. Lublin, G. Giovannoni, A. Wajgt, et al. 2006. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 354:899-910. http://dx.doi.org/10.1056/NEJMoa044397.
50. Racke, M.K., A. Bonomo, D.E. Scott, B. Cannella, A. Levine, C.S. Raine, E.M. Shevach, and M. Röcken. 1994. Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease. J. Exp. Med. 180:1961-1966. http://dx.doi.org/10.1084/jem.180.5.1961.
51. Rothfuss, O., H. Fischer, T. Hasegawa, M. Maisel, P. Leitner, F. Miesel, M. Sharma, A. Bornemann, D. Berg, T. Gasser, and N. Patenge. 2009. Parkin protects mitochondrial genome integrity and supports mitochondrial DNA repair. Hum. Mol. Genet. 18:3832-3850. http://dx.doi.org/10.1093/hmg/ddp327.
52. Schilling, S., S. Goelz, R. Linker, F. Luehder, and R. Gold. 2006. Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infiltration. Clin. Exp. Immunol. 145:101-107. http://dx.doi.org/10.1111/j.1365-2249.2006.03094.x.
53. Schuler, G., B. Schuler-Thurner, and R.M. Steinman. 2003. The use of dendritic cells in cancer immunotherapy. Curr. Opin. Immunol. 15:138-147. http://dx.doi.org/10.1016/S0952-7915(03)00015-3.
54. Segal, B.M., C.S. Constantinescu, A. Raychaudhuri, L. Kim, R. Fidelus-Gort, and L.H. Kasper. 2008. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsingremitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol. 7:796-804. http://dx.doi.org/10.1016/S1474-4422(08)70173-X.
55. Tzima, S., P. Victoratos, K. Kranidioti, M. Alexiou, and G. Kollias. 2009. Myeloid heme oxygenase-1 regulates innate immunity and autoimmunity by modulating IFN-β production. J. Exp. Med. 206:1167-1179. http://dx.doi.org/10.1084/jem.20081582.
56. Weber, M.S., T. Prod'homme, S. Youssef, S.E. Dunn, C.D. Rundle, L. Lee, J.C. Patarroyo, O. Stüve, R.A. Sobel, L. Steinman, and S.S. Zamvil. 2007. Type II monocytes modulate T cell-mediated central nervous system autoimmune disease. Nat. Med. 13:935-943. http://dx.doi.org/10.1038/nm1620.
57. Zhu, C., K. Rao, H. Xiong, K. Gagnidze, F. Li, C. Horvath, and S. Plevy. 2003. Activation of the murine interleukin-12 p40 promoter by functional interactions between NFAT and ICSBP. J. Biol. Chem. 278:39372-39382. http://dx.doi.org/10.1074/jbc.M306441200