Role for MyD88, TLR2 and TLR9 but not TLR1, TLR4 or TLR6 in experimental autoimmune encephalomyelitis

Journal of Immunology

Volumn 187, Issue 2, 2011, Pages 791-804

  Miranda Hernandez, Socorro ^a   Gerlach, Nicole ^a   Fletcher, Julie M ^a   Biros, Erik ^a   Mack, Matthias ^b   Körner, Heinrich ^a   Baxter, Alan G ^a  

^a JAMES COOK UNIVERSITY   (Australia)

^b UNIVERSITY HOSPITAL REGENSBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEIN; GLYCOPROTEIN [35-55]; INTERLEUKIN 6; L SELECTIN; MYELIN; MYELOID DIFFERENTIATION FACTOR 88; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 6; TOLL LIKE RECEPTOR 9; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; CYTOKINE PRODUCTION; DISEASE PREDISPOSITION; DISEASE SEVERITY; FEMALE; IMMUNOPATHOGENESIS; LEUKOCYTE; LYMPHOCYTIC INFILTRATION; MALE; MOUSE; NONHUMAN; OLIGODENDROGLIA; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN TARGETING; REGULATORY T LYMPHOCYTE; SCORING SYSTEM; SIGNAL TRANSDUCTION;

ANIMALS; CELL MOVEMENT; CELLS, CULTURED; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; GENE SILENCING; GENETIC PREDISPOSITION TO DISEASE; GLYCOPROTEINS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MYELOID DIFFERENTIATION FACTOR 88; NERVE TISSUE PROTEINS; PEPTIDE FRAGMENTS; SEVERITY OF ILLNESS INDEX; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 1; TOLL-LIKE RECEPTOR 2; TOLL-LIKE RECEPTOR 4; TOLL-LIKE RECEPTOR 6; TOLL-LIKE RECEPTOR 9;

EID: 79960536837     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1001992     Document Type: Article

References (91)

1. Sawcer, S. 2008. The complex genetics of multiple sclerosis: pitfalls and prospects. Brain 131: 3118-3131.
2. Strachan, D. P. 1989. Hay fever, hygiene, and household size. BMJ 299: 1259-1260. (Pubitemid 19280051)
3. van den Biggelaar, A. H., L. C. Rodrigues, R. van Ree, J. S. van der Zee, Y. C. Hoeksma-Kruize, J. H. Souverijn, M. A. Missinou, S. Borrmann, P. G. Kremsner, and M. Yazdanbakhsh. 2004. Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren. J. Infect. Dis. 189: 892-900.
4. Shaheen, S. O., P. Aaby, A. J. Hall, D. J. Barker, C. B. Heyes, A. W. Shiell, and A. Goudiaby. 1996. Measles and atopy in Guinea-Bissau. Lancet 347: 1792-1796. (Pubitemid 26323329)
5. Rook, G. A., and J. L. Stanford. 1998. Give us this day our daily germs. Immunol. Today 19: 113-116.
6. Rook, G. A., G. Ristori, M. Salvetti, G. Giovannoni, E. J. Thompson, and J. L. Stanford. 2000. Bacterial vaccines for the treatment of multiple sclerosis and other autoimmune disorders. Immunol. Today 21: 503-508.
7. Sheikh, A., L. Smeeth, and R. Hubbard. 2003. There is no evidence of an inverse relationship between TH2-mediated atopy and TH1-mediated autoimmune disorders: lack of support for the hygiene hypothesis. J. Allergy Clin. Immunol. 111: 131-135.
8. Ristori, G., M. G. Buzzi, U. Sabatini, E. Giugni, S. Bastianello, F. Viselli, C. Buttinelli, S. Ruggieri, C. Colonnese, C. Pozzilli, and M. Salvetti. 1999. Use of Bacille Calmette-Guèrin (BCG) in multiple sclerosis. Neurology 53: 1588-1589. (Pubitemid 29491961)
9. Shehadeh, N., F. Calcinaro, B. J. Bradley, I. Bruchim, P. Vardi, and K. J. Lafferty. 1994. Effect of adjuvant therapy on development of diabetes in mouse and man. [Published erratum appears in 2006 Lancet 367: 1240.] Lancet 343: 706-707. (Pubitemid 24087852)
10. Baxter, A. G., A. C. Horsfall, D. Healey, P. Ozegbe, S. Day, D. G. Williams, and A. Cooke. 1994. Mycobacteria precipitate an SLE-like syndrome in diabetesprone NOD mice. Immunology 83: 227-231. (Pubitemid 24315591)
11. Jordan, M. A., P. A. Silveira, D. P. Shepherd, C. Chu, S. J. Kinder, J. Chen, L. J. Palmisano, L. D. Poulton, and A. G. Baxter. 2000. Linkage analysis of systemic lupus erythematosus induced in diabetes-prone nonobese diabetic mice by Mycobacterium bovis. J. Immunol. 165: 1673-1684.
12. Silveira, P. A., and A. G. Baxter. 2001. The NOD mouse as a model of SLE. Autoimmunity 34: 53-64.
13. Janeway, C. A., Jr., and R. Medzhitov. 2002. Innate immune recognition. Annu. Rev. Immunol. 20: 197-216.
14. Medzhitov, R., P. Preston-Hurlburt, and C. A. Janeway Jr. 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394-397.
15. Ausubel, F. M. 2005. Are innate immune signaling pathways in plants and animals conserved? Nat. Immunol. 6: 973-979. (Pubitemid 41486181)
16. Kumar, H., T. Kawai, and S. Akira. 2009. Toll-like receptors and innate immunity. Biochem. Biophys. Res. Commun. 388: 621-625.
17. Yoshimura, A., E. Lien, R. R. Ingalls, E. Tuomanen, R. Dziarski, and D. Golenbock. 1999. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J. Immunol. 163: 1-5. (Pubitemid 29295815)
18. Schwandner, R., R. Dziarski, H. Wesche, M. Rothe, and C. J. Kirschning. 1999. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J. Biol. Chem. 274: 17406-17409.
19. Takeuchi, O., K. Hoshino, T. Kawai, H. Sanjo, H. Takada, T. Ogawa, K. Takeda, and S. Akira. 1999. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 11: 443-451. (Pubitemid 29504199)
20. Poltorak, A., X. He, I. Smirnova, M. Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, et al. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282: 2085-2088. (Pubitemid 29001265)
21. Hayashi, F., K. D. Smith, A. Ozinsky, T. R. Hawn, E. C. Yi, D. R. Goodlett, J. K. Eng, S. Akira, D. M. Underhill, and A. Aderem. 2001. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410: 1099-1103. (Pubitemid 32391041)
22. Ozinsky, A., D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith, C. B. Wilson, L. Schroeder, and A. Aderem. 2000. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc. Natl. Acad. Sci. USA 97: 13766-13771.
23. Wyllie, D. H., E. Kiss-Toth, A. Visintin, S. C. Smith, S. Boussouf, D. M. Segal, G. W. Duff, and S. K. Dower. 2000. Evidence for an accessory protein function for Toll-like receptor 1 in anti-bacterial responses. J. Immunol. 165: 7125-7132.
24. Hajjar, A. M., D. S. O'Mahony, A. Ozinsky, D. M. Underhill, A. Aderem, S. J. Klebanoff, and C. B. Wilson. 2001. Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin. J. Immunol. 166: 15-19.
25. Kawai, T., and S. Akira. 2005. Pathogen recognition with Toll-like receptors. Curr. Opin. Immunol. 17: 338-344.
26. Hemmi, H., O. Takeuchi, T. Kawai, T. Kaisho, S. Sato, H. Sanjo, M. Matsumoto, K. Hoshino, H. Wagner, K. Takeda, and S. Akira. 2000. A Toll-like receptor recognizes bacterial DNA. Nature 408: 740-745. [Published erratum appears in 2001 Nature 409: 646.]
27. Bever, C. T., Jr., A. M. Salazar, E. Neely, B. E. Ferraraccio, J. W. Rose, H. F. McFarland, H. B. Levy, and D. E. McFarlin. 1986. Preliminary trial of poly ICLC in chronic progressive multiple sclerosis. Neurology 36: 494-498.
28. Touil, T., D. Fitzgerald, G. X. Zhang, A. Rostami, and B. Gran. 2006. Cutting Edge: TLR3 stimulation suppresses experimental autoimmune encephalomyelitis by inducing endogenous IFN-beta. J. Immunol. 177: 7505-7509. (Pubitemid 44846263)
29. Panitch, H. S., R. L. Hirsch, A. S. Haley, and K. P. Johnson. 1987. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 329: 893-895.
30. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. 1999. TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology 53: 457-465.
31. Mohan, N., E. T. Edwards, T. R. Cupps, P. J. Oliverio, G. Sandberg, H. Crayton, J. R. Richert, and J. N. Siegel. 2001. Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum. 44: 2862-2869.
32. Prinz, M., F. Garbe, H. Schmidt, A. Mildner, I. Gutcher, K. Wolter, M. Piesche, R. Schroers, E. Weiss, C. J. Kirschning, et al. 2006. Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis. J. Clin. Invest. 116: 456-464.
33. Marta, M., A. Andersson, M. Isaksson, O. Kämpe, and A. Lobell. 2008. Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis. Eur. J. Immunol. 38: 565-575.
34. Kerfoot, S. M., E. M. Long, M. J. Hickey, G. Andonegui, B. M. Lapointe, R. C. O. Zanardo, C. Bonder, W. G. James, S. M. Robbins, and P. Kubes. 2004. TLR4 contributes to disease-inducing mechanisms resulting in central nervous system autoimmune disease. J. Immunol. 173: 7070-7077. (Pubitemid 39541097)
35. Reynolds, J. M., B. P. Pappu, J. Peng, G. J. Martinez, Y. Zhang, Y. Chung, L. Ma, X. O. Yang, R. I. Nurieva, Q. Tian, and C. Dong. 2010. Toll-like receptor 2 signaling in CD4(+) T lymphocytes promotes T helper 17 responses and regulates the pathogenesis of autoimmune disease. Immunity 32: 692-702.
36. Adachi, O., T. Kawai, K. Takeda, M. Matsumoto, H. Tsutsui, M. Sakagami, K. Nakanishi, and S. Akira. 1998. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9: 143-150. (Pubitemid 28361303)
37. Hoshino, K., O. Takeuchi, T. Kawai, H. Sanjo, T. Ogawa, Y. Takeda, K. Takeda, and S. Akira. 1999. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J. Immunol. 162: 3749-3752. (Pubitemid 29314747)
38. Takeuchi, O., T. Kawai, P. F. Mühlradt, M. Morr, J. D. Radolf, A. Zychlinsky, K. Takeda, and S. Akira. 2001. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int. Immunol. 13: 933-940.
39. Takeuchi, O., S. Sato, T. Horiuchi, K. Hoshino, K. Takeda, Z. Dong, R. L. Modlin, and S. Akira. 2002. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 169: 10-14. (Pubitemid 34686113)
40. Humason, G. H. 1972. Animal Tissue Techniques. W.H. Freeman & Company, San Franscisco, p. 238-239.
41. Hempel, K., A. Freitag, B. Freitag, B. Endres, B. Mai, and G. Liebaldt. 1985. Unresponsiveness to experimental allergic encephalomyelitis in Lewis rats pretreated with complete Freund's adjuvant. Int. Arch. Allergy Appl. Immunol. 76: 193-199.
42. Ford, A. L., A. L. Goodsall, W. F. Hickey, and J. D. Sedgwick. 1995. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J. Immunol. 154: 4309-4321.
43. Mack, M., J. Cihak, C. Simonis, B. Luckow, A. E. Proudfoot, J. Plachý, H. Brühl, M. Frink, H. J. Anders, V. Vielhauer, et al. 2001. Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice. J. Immunol. 166: 4697-4704. (Pubitemid 32233757)
44. Gururajan, M., J. Jacob, and B. Pulendran. 2007. Toll-like receptor expression and responsiveness of distinct murine splenic and mucosal B-cell subsets. PLoS ONE 2: e863.
45. Brightbill, H. D., D. H. Libraty, S. R. Krutzik, R. B. Yang, J. T. Belisle, J. R. Bleharski, M. Maitland, M. V. Norgard, S. E. Plevy, S. T. Smale, et al. 1999. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285: 732-736.
46. Jones, B. W., T. K. Means, K. A. Heldwein, M. A. Keen, P. J. Hill, J. T. Belisle, and M. J. Fenton. 2001. Different Toll-like receptor agonists induce distinct macrophage responses. J. Leukoc. Biol. 69: 1036-1044.
47. Means, T. K., S. Wang, E. Lien, A. Yoshimura, D. T. Golenbock, and M. J. Fenton. 1999. Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. J. Immunol. 163: 3920-3927.
48. Thoma-Uszynski, S., S. M. Kiertscher, M. T. Ochoa, D. A. Bouis, M. V. Norgard, K. Miyake, P. J. Godowski, M. D. Roth, and R. L. Modlin. 2000. Activation of toll-like receptor 2 on human dendritic cells triggers induction of IL-12, but not IL-10. J. Immunol. 165: 3804-3810.
49. Abel, B., N. Thieblemont, V. J. Quesniaux, N. Brown, J.Mpagi, K.Miyake, F. Bihl, and B. Ryffel. 2002. Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice. J. Immunol. 169: 3155-3162. (Pubitemid 35013161)
50. Bafica, A., C. A. Scanga, C. G. Feng, C. Leifer, A. Cheever, and A. Sher. 2005. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J. Exp. Med. 202: 1715-1724.
51. Apetoh, L., F. Ghiringhelli, A. Tesniere, M. Obeid, C. Ortiz, A. Criollo, G. Mignot, M. C. Maiuri, E. Ullrich, P. Saulnier, et al. 2007. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13: 1050-1059.
52. Paulos, C. M., C. Wrzesinski, A. Kaiser, C. S. Hinrichs, M. Chieppa, L. Cassard, D. C. Palmer, A. Boni, P. Muranski, Z. Yu, et al. 2007. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J. Clin. Invest. 117: 2197-2204.
53. Fife, B. T., G. B. Huffnagle, W. A. Kuziel, and W. J. Karpus. 2000. CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J. Exp. Med. 192: 899-905.
54. Izikson, L., R. S. Klein, I. F. Charo, H. L. Weiner, and A. D. Luster. 2000. Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J. Exp. Med. 192: 1075-1080.
55. Mahad, D., M. K. Callahan, K. A. Williams, E. E. Ubogu, P. Kivisäkk, B. Tucky, G. Kidd, G. A. Kingsbury, A. Chang, R. J. Fox, et al. 2006. Modulating CCR2 and CCL2 at the blood-brain barrier: relevance for multiple sclerosis pathogenesis. Brain 129: 212-223. (Pubitemid 43063772)
56. Kohm, A. P., P. A. Carpentier, H. A. Anger, and S. D. Miller. 2002. Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 169: 4712-4716.
57. Szanya, V., J. Ermann, C. Taylor, C. Holness, and C. G. Fathman. 2002. The subpopulation of CD4+CD25+ splenocytes that delays adoptive transfer of diabetes expresses L-selectin and high levels of CCR7. J. Immunol. 169: 2461-2465.
58. Taylor, P. A., A. Panoskaltsis-Mortari, J. M. Swedin, P. J. Lucas, R. E. Gress, B. L. Levine, C. H. June, J. S. Serody, and B. R. Blazar. 2004. L-Selectin(hi) but not the L-selectin(lo) CD4+25+ T-regulatory cells are potent inhibitors of GVHD and BM graft rejection. Blood 104: 3804-3812.
59. Ermann, J., P. Hoffmann, M. Edinger, S. Dutt, F. G. Blankenberg, J. P. Higgins, R. S. Negrin, C. G. Fathman, and S. Strober. 2005. Only the CD62L+ sub-population of CD4+CD25+ regulatory T cells protects from lethal acute GVHD. Blood 105: 2220-2226. (Pubitemid 40731816)
60. Baxter, A. G. 2007. The origin and application of experimental autoimmune encephalomyelitis. Nat. Rev. Immunol. 7: 904-912.
61. Hansen, B. S., R. Z. Hussain, A. E. Lovett-Racke, J. A. Thomas, and M. K. Racke. 2006. Multiple toll-like receptor agonists act as potent adjuvants in the induction of autoimmunity. J. Neuroimmunol. 172: 94-103.
62. Segal, B. M., J. T. Chang, and E. M. Shevach. 2000. CpG oligonucleotides are potent adjuvants for the activation of autoreactive encephalitogenic T cells in vivo. J. Immunol. 164: 5683-5688.
63. Wolf, N. A., T. K. Amouzegar, and R. H. Swanborg. 2007. Synergistic interaction between Toll-like receptor agonists is required for induction of experimental autoimmune encephalomyelitis in Lewis rats. J. Neuroimmunol. 185: 115-122.
64. Tigno-Aranjuez, J. T., R. Jaini, V. K. Tuohy, P. V. Lehmann, and M. Tary-Lehmann. 2009. Encephalitogenicity of complete Freund's adjuvant relative to CpG is linked to induction of Th17 cells. J. Immunol. 183: 5654-5661.
65. Nagasawa, K., R. Mori, S. Kondo, and K. Hisatsune. 1979. Correlation between the capacity of bacterial lipopolysaccharide to supress experimental allergic encephalomyelitis and its mitogenic activity for lymph node cells in guinea pigs. J. Neurol. Sci. 42: 417-427.
66. Buenafe, A. C., and D. N. Bourdette. 2007. Lipopolysaccharide pretreatment modulates the disease course in experimental autoimmune encephalomyelitis. J. Neuroimmunol. 182: 32-40.
67. Lampropoulou, V., K. Hoehlig, T. Roch, P. Neves, E. Calderón Gómez, C. H. Sweenie, Y. Hao, A. A. Freitas, U. Steinhoff, S. M. Anderton, and S. Fillatreau. 2008. TLR-activated B cells suppress T cell-mediated autoimmunity. J. Immunol. 180: 4763-4773.
68. Buwitt-Beckmann, U., H. Heine, K. H. Wiesmüller, G. Jung, R. Brock, S. Akira, and A. J. Ulmer. 2006. TLR1- and TLR6-independent recognition of bacterial lipopeptides. J. Biol. Chem. 281: 9049-9057.
69. Ellestad, K. K., S. Tsutsui, F. Noorbakhsh, K. G. Warren, V. W. Yong, Q. J. Pittman, and C. Power. 2009. Early life exposure to lipopolysaccharide suppresses experimental autoimmune encephalomyelitis by promoting tolero-genic dendritic cells and regulatory T cells. J. Immunol. 183: 298-309.
70. Greisman, S. E., and W. E. Woodward. 1965. Mechanisms of endotoxin tolerance. 3. The refractory state during continuous intravenous infusions of endotoxin. J. Exp. Med. 121: 911-933.
71. Su, S. B., P. B. Silver, R. S. Grajewski, R. K. Agarwal, J. Tang, C. C. Chan, and R. R. Caspi. 2005. Essential role of the MyD88 pathway, but nonessential roles of TLRs 2, 4, and 9, in the adjuvant effect promoting Th1-mediated autoimmunity. J. Immunol. 175: 6303-6310.
72. Lamason, R., P. Zhao, R. Rawat, A. Davis, J. C. Hall, J. J. Chae, R. Agarwal, P. Cohen, A. Rosen, E. P. Hoffman, and K. Nagaraju. 2006. Sexual dimorphism in immune response genes as a function of puberty. BMC Immunol. 7: 2.
73. Keith, A. B. 1978. Sex difference in Lewis rats in the incidence of recurrent experimental allergic encephalomyelitis. Nature 272: 824-825. (Pubitemid 8316988)
74. Bebo, B. F., Jr., A. A. Vandenbark, and H. Offner. 1996. Male SJL mice do not relapse after induction of EAE with PLP 139-151. J. Neurosci. Res. 45: 680-689.
75. Trooster, W. J., A. W. Teelken, P. O. Gerrits, T. H. Lijnema, J. G. Loof, J. M. Minderhoud, and P. Nieuwenhuis. 1996. The effect of gonadectomy on the clinical course of chronic experimental allergic encephalomyelitis. Clin. Neurol. Neurosurg. 98: 222-226.
76. Voskuhl, R. R., H. Pitchekian-Halabi, A. MacKenzie-Graham, H. F. McFarland, and C. S. Raine. 1996. Gender differences in autoimmune demyelination in the mouse: implications for multiple sclerosis. Ann. Neurol. 39: 724-733.
77. Orton, S. M., S. V. Ramagopalan, D. Brocklebank, B. M. Herrera, D. A. Dyment, I. M. Yee, A. D. Sadovnick, and G. C. Ebers. 2010. Effect of immigration on multiple sclerosis sex ratio in Canada: the Canadian Collaborative Study. J. Neurol. Neurosurg. Psychiatry 81: 31-36.
78. Erridge, C. 2010. Endogenous ligands of TLR2 and TLR4: agonists or assistants? J. Leukoc. Biol. 87: 989-999.
79. Erridge, C., T. Attina, C. M. Spickett, and D. J. Webb. 2007. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am. J. Clin. Nutr. 86: 1286-1292.
80. Clarke, T. B., K. M. Davis, E. S. Lysenko, A. Y. Zhou, Y. Yu, and J. N. Weiser. 2010. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat. Med. 16: 228-231.
81. Iwaki, D., H. Mitsuzawa, S. Murakami, H. Sano, M. Konishi, T. Akino, and Y. Kuroki. 2002. The extracellular toll-like receptor 2 domain directly binds peptidoglycan derived from Staphylococcus aureus. J. Biol. Chem. 277: 24315-24320.
82. Dziarski, R., and D. Gupta. 2005. Staphylococcus aureus peptidoglycan is a toll-like receptor 2 activator: a reevaluation. Infect. Immun. 73: 5212-5216.
83. Kumar, V., K. Stellrecht, and E. Sercarz. 1996. Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE). J. Exp. Med. 184: 1609-1617. (Pubitemid 26404454)
84. McGeachy, M. J., L. A. Stephens, and S. M. Anderton. 2005. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system. J. Immunol. 175: 3025-3032.
85. Yu, P., R. K. Gregg, J. J. Bell, J. S. Ellis, R. Divekar, H. H. Lee, R. Jain, H. Waldner, J. C. Hardaway, M. Collins, et al. 2005. Specific T regulatory cells display broad suppressive functions against experimental allergic encephalomyelitis upon activation with cognate antigen. J. Immunol. 174: 6772-6780. (Pubitemid 40705640)
86. Selvaraj, R. K., and T. L. Geiger. 2008. Mitigation of experimental allergic encephalomyelitis by TGF-beta induced Foxp3+ regulatory T lymphocytes through the induction of anergy and infectious tolerance. J. Immunol. 180: 2830-2838.
87. Stephens, L. A., K. H. Malpass, and S. M. Anderton. 2009. Curing CNS auto-immune disease with myelin-reactive Foxp3+ Treg. Eur. J. Immunol. 39: 1108-1117.
88. Zhang, X., D. N. Koldzic, L. Izikson, J. Reddy, R. F. Nazareno, S. Sakaguchi, V. K. Kuchroo, and H. L. Weiner. 2004. IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells. Int. Immunol. 16: 249-256.
89. Dominitzki, S., M. C. Fantini, C. Neufert, A. Nikolaev, P. R. Galle, J. Scheller, G. Monteleone, S. Rose-John, M. F. Neurath, and C. Becker. 2007. Cutting edge: trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25 T cells. J. Immunol. 179: 2041-2045.
90. Xiao, W., D. R. Hodge, L. Wang, X. Yang, X. Zhang, and W. L. Farrar. 2004. Cooperative functions between nuclear factors NFkappaB and CCAT/enhancerbinding protein-beta (C/EBP-beta) regulate the IL-6 promoter in autocrine human prostate cancer cells. Prostate 61: 354-370.
91. Samoilova, E. B., J. L. Horton, B. Hilliard, T. S. Liu, and Y. Chen. 1998. IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. J. Immunol. 161: 6480-6486. (Pubitemid 28562184)