TLR4 signaling via MyD88 and TRIF differentially shape the CD4+ T cell response to Porphyromonas gingivalis hemagglutinin B

Journal of Immunology

Volumn 186, Issue 10, 2011, Pages 5772-5783

  Gaddis, Dalia E ^a   Michalek, Suzanne M ^a   Katz, Jannet ^b  

^a University of Alabama at Birmingham   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEMAGGLUTININ; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G2; INTERLEUKIN 2; MYELOID DIFFERENTIATION FACTOR 88; STAT5 PROTEIN; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR ADAPTOR MOLECULE 1; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR GATA 3;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIBODY RESPONSE; ARTICLE; CD4+ T LYMPHOCYTE; CELL ISOLATION; CELLULAR IMMUNITY; CONTROLLED STUDY; FEMALE; IMMUNIZATION; IMMUNOGLOBULIN BLOOD LEVEL; LYMPHOCYTE ACTIVATION; MOUSE; NONHUMAN; PORPHYROMONAS GINGIVALIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; WILD TYPE;

ADAPTOR PROTEINS, VESICULAR TRANSPORT; ADHESINS, BACTERIAL; ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; DENDRITIC CELLS; FORKHEAD TRANSCRIPTION FACTORS; GATA3 TRANSCRIPTION FACTOR; IMMUNOGLOBULIN G; INTERFERON-GAMMA; INTERLEUKIN-17; INTERLEUKIN-2; LECTINS; LYMPHOCYTE ACTIVATION; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MYELOID DIFFERENTIATION FACTOR 88; PORPHYROMONAS GINGIVALIS; SIGNAL TRANSDUCTION; STAT5 TRANSCRIPTION FACTOR; TH1 CELLS; TH2 CELLS; TOLL-LIKE RECEPTOR 4;

EID: 79956199473     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1003192     Document Type: Article

References (97)

1. Lamont, R. J., and H. F. Jenkinson. 1998. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol. Mol. Biol. Rev. 62: 1244-1263.
2. Socransky, S. S., A. D. Haffajee, M. A. Cugini, C. Smith, and R. L. Kent, Jr. 1998. Microbial complexes in subgingival plaque. J. Clin. Periodontol. 25: 134-144.
3. Slots, J., L. Bragd, M. Wikström, and G. Dahlén. 1986. The occurrence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius in destructive periodontal disease in adults. J. Clin. Periodontol. 13: 570-577.
4. López, N. J. 2000. Occurrence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia in progressive adult periodontitis. J. Periodontol. 71: 948-954.
5. Beck, J., R. Garcia, G. Heiss, P. S. Vokonas, and S. Offenbacher. 1996. Periodontal disease and cardiovascular disease. J. Periodontol. 67(10, Suppl)1123-1137. (Pubitemid 126613093)
6. Craig, R. G. 2004. Inflammation, cardiovascular disease and destructive periodontal diseases: the evolving role of the dental profession. N. Y. State Dent. J. 70: 22-26.
7. Craig, R. G., P. Kotanko, A. R. Kamer, and N. W. Levin. 2007. Periodontal diseases: a modifiable source of systemic inflammation for the end-stage renal disease patient on haemodialysis therapy? Nephrol. Dial. Transplant. 22: 312-315.
8. Offenbacher, S., V. Katz, G. Fertik, J. Collins, D. Boyd, G. Maynor, R. McKaig, and J. Beck. 1996. Periodontal infection as a possible risk factor for preterm low birth weight. J. Periodontol. 67(10, Suppl.): 1103-1113. (Pubitemid 126613091)
9. Gemmell, E., K. Yamazaki, and G. J. Seymour. 2007. The role of T cells in periodontal disease: homeostasis and autoimmunity. Periodontol. 2000 43: 14-40.
10. Duncan, M. J., S. Nakao, Z. Skobe, and H. Xie. 1993. Interactions of Porphyromonas gingivalis with epithelial cells. Infect. Immun. 61: 2260-2265.
11. Hirose, K., E. Isogai, H. Mizugai, and I. Ueda. 1996. Adhesion of Porphyromonas gingivalis fimbriae to human gingival cell line Ca9-22. Oral Microbiol. Immunol. 11: 402-406.
12. Kuramitsu, H. K. 1998. Proteases of Porphyromonas gingivalis: what don't they do? Oral Microbiol. Immunol. 13: 263-270. (Pubitemid 28443765)
13. Oleksy, A., A. Banbula, M. Bugno, J. Travis, and J. Potempa. 2002. Proteolysis of interleukin-6 receptor (IL-6R) by Porphyromonas gingivalis cysteine proteinases (gingipains) inhibits interleukin-6-mediated cell activation. Microb. Pathog. 32: 173-181.
14. Potempa, J., A. Banbula, and J. Travis. 2000. Role of bacterial proteinases in matrix destruction and modulation of host responses. Periodontol. 2000 24: 153-192.
15. Zhang, J., H. Dong, S. Kashket, and M. J. Duncan. 1999. IL-8 degradation by Porphyromonas gingivalis proteases. Microb. Pathog. 26: 275-280.
16. Minnick, M. F., R. A. Rupp, and K. D. Spence. 1986. A bacterial-induced lectin which triggers hemocyte coagulation in Manduca sexta. Biochem. Biophys. Res. Commun. 137: 729-735.
17. Lépine, G., R. P. Ellen, and A. Progulske-Fox. 1996. Construction and preliminary characterization of three hemagglutinin mutants of Porphyromonas gingivalis. Infect. Immun. 64: 1467-1472.
18. Lépine, G., and A. Progulske-Fox. 1996. Duplication and differential expression of hemagglutinin genes in Porphyromonas gingivalis. Oral Microbiol. Immunol. 11: 65-78.
19. Progulske-Fox, A., S. Tumwasorn, and S. C. Holt. 1989. The expression and function of a Bacteroides gingivalis hemagglutinin gene in Escherichia coli. Oral Microbiol. Immunol. 4: 121-131.
20. Progulske-Fox, A., S. Tumwasorn, G. Lépine, J. Whitlock, D. Savett, J. J. Ferretti, and J. A. Banas. 1995. The cloning, expression and sequence analysis of a second Porphyromonas gingivalis gene that codes for a protein involved in hemagglutination. Oral Microbiol. Immunol. 10: 311-318.
21. Zhang, P., M. Martin, S. M. Michalek, and J. Katz. 2005. Role of mitogen-activated protein kinases and NF-κB in the regulation of proinflammatory and anti-inflammatory cytokines by Porphyromonas gingivalis hemagglutinin B. Infect. Immun. 73: 3990-3998.
22. Gaddis, D. E., S. M. Michalek, and J. Katz. 2009. Requirement of TLR4 and CD14 in dendritic cell activation by hemagglutinin B from Porphyromonas gingivalis. Mol. Immunol. 46: 2493-2504.
23. Dusek, D. M., A. Progulske-Fox, and T. A. Brown. 1994. Systemic and mucosal immune responses in mice orally immunized with avirulent Salmonella typhimurium expressing a cloned Porphyromonas gingivalis hemagglutinin. Infect. Immun. 62: 1652-1657.
24. Dusek, D. M., A. Progulske-Fox, J. Whitlock, and T. A. Brown. 1993. Isolation and characterization of a cloned Porphyromonas gingivalis hemagglutinin from an avirulent strain of Salmonella typhimurium. Infect. Immun. 61: 940-946.
25. Katz, J., K. P. Black, and S. M. Michalek. 1999. Host responses to recombinant hemagglutinin B of Porphyromonas gingivalis in an experimental rat model. Infect. Immun. 67: 4352-4359.
26. Yang, Q. B., M. Martin, S. M. Michalek, and J. Katz. 2002. Mechanisms of monophosphoryl lipid A augmentation of host responses to recombinant HagB from Porphyromonas gingivalis. Infect. Immun. 70: 3557-3565.
27. Zhang, P., M. Martin, Q. B. Yang, S. M. Michalek, and J. Katz. 2004. Role of B7 costimulatory molecules in immune responses and T-helper cell differentiation in response to recombinant HagB from Porphyromonas gingivalis. Infect. Immun. 72: 637-644.
28. Zhang, P., Q. B. Yang, D. J. Marciani, M. Martin, J. D. Clements, S. M. Michalek, and J. Katz. 2003. Effectiveness of the quillaja saponin semisynthetic analog GPI-0100 in potentiating mucosal and systemic responses to recombinant HagB from Porphyromonas gingivalis. Vaccine 21: 4459-4471. (Pubitemid 37130284)
29. Song, H., M. Bélanger, J. Whitlock, E. Kozarov, and A. Progulske-Fox. 2005. Hemagglutinin B is involved in the adherence of Porphyromonas gingivalis to human coronary artery endothelial cells. Infect. Immun. 73: 7267-7273.
30. O'Neill, L. A. 2006. How Toll-like receptors signal: what we know and what we don't know. Curr. Opin. Immunol. 18: 3-9.
31. O'Neill, L. A., K. A. Fitzgerald, and A. G. Bowie. 2003. The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol. 24: 286-290.
32. Takeda, K., and S. Akira. 2005. Toll-like receptors in innate immunity. Int. Immunol. 17: 1-14.
33. Rassa, J. C., J. L. Meyers, Y. Zhang, R. Kudaravalli, and S. R. Ross. 2002. Murine retroviruses activate B cells via interaction with Toll-like receptor 4. Proc. Natl. Acad. Sci. USA 99: 2281-2286.
34. Ashtekar, A. R., P. Zhang, J. Katz, C. C. Deivanayagam, P. Rallabhandi, S. N. Vogel, and S. M. Michalek. 2008. TLR4-mediated activation of dendritic cells by the heat shock protein DnaK from Francisella tularensis. J. Leukoc. Biol. 84: 1434-1446.
35. Bulut, Y., K. S. Michelsen, L. Hayrapetian, Y. Naiki, R. Spallek, M. Singh, and M. Arditi. 2005. Mycobacterium tuberculosis heat shock proteins use diverse Toll-like receptor pathways to activate pro-inflammatory signals. J. Biol. Chem. 280: 20961-20967.
36. Cohen-Sfady, M., G. Nussbaum, M. Pevsner-Fischer, F. Mor, P. Carmi, A. Zanin-Zhorov, O. Lider, and I. R. Cohen. 2005. Heat shock protein 60 activates B cells via the TLR4-MyD88 pathway. J. Immunol. 175: 3594-3602.
37. 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.
38. Yamamoto, M., S. Sato, K. Mori, K. Hoshino, O. Takeuchi, K. Takeda, and S. Akira. 2002. Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-β promoter in the Toll-like receptor signaling. J. Immunol. 169: 6668-6672. (Pubitemid 36899248)
39. Yamamoto, M., S. Sato, H. Hemmi, K. Hoshino, T. Kaisho, H. Sanjo, O. Takeuchi, M. Sugiyama, M. Okabe, K. Takeda, and S. Akira. 2003. Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway. Science 301: 640-643. (Pubitemid 36927946)
40. Takeda, K., and S. Akira. 2004. TLR signaling pathways. Semin. Immunol. 16: 3-9.
41. Hoebe, K., X. Du, P. Georgel, E. Janssen, K. Tabeta, S. O. Kim, J. Goode, P. Lin, N. Mann, S. Mudd, et al. 2003. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424: 743-748. (Pubitemid 37021696)
42. Barton, G. M., and R. Medzhitov. 2002. Control of adaptive immune responses by Toll-like receptors. Curr. Opin. Immunol. 14: 380-383.
43. Kabelitz, D., and R. Medzhitov. 2007. Innate immunity: cross-talk with adaptive immunity through pattern recognition receptors and cytokines. Curr. Opin. Immunol. 19: 1-3.
44. Schnare, M., G. M. Barton, A. C. Holt, K. Takeda, S. Akira, and R. Medzhitov. 2001. Toll-like receptors control activation of adaptive immune responses. Nat. Immunol. 2: 947-950.
45. Pasare, C., and R. Medzhitov. 2004. Toll-like receptors: linking innate and adaptive immunity. Microbes Infect. 6: 1382-1387. (Pubitemid 41110581)
46. Pasare, C., and R. Medzhitov. 2004. Toll-dependent control mechanisms of CD4 T cell activation. Immunity 21: 733-741. (Pubitemid 39487894)
47. Pasare, C., and R. Medzhitov. 2004. Toll-like receptors and acquired immunity. Semin. Immunol. 16: 23-26.
48. Mazzoni, A., and D. M. Segal. 2004. Controlling the Toll road to dendritic cell polarization. J. Leukoc. Biol. 75: 721-730.
49. Manicassamy, S., and B. Pulendran. 2009. Modulation of adaptive immunity with Toll-like receptors. Semin. Immunol. 21: 185-193.
50. Iwasaki, A., and R. Medzhitov. 2004. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5: 987-995.
51. Owens, T., and R. Zeine. 1989. The cell biology of T-dependent B cell activation. Biochem. Cell Biol. 67: 481-489.
52. Bourgeois, C., and C. Tanchot. 2003. Mini-review CD4 T cells are required for CD8 T cell memory generation. Eur. J. Immunol. 33: 3225-3231.
53. Ma, J., T. Chen, J. Mandelin, A. Ceponis, N. E. Miller, M. Hukkanen, G. F. Ma, and Y. T. Konttinen. 2003. Regulation of macrophage activation. Cell. Mol. Life Sci. 60: 2334-2346.
54. Zhu, J., and W. E. Paul. 2008. CD4 T cells: fates, functions, and faults. Blood 112: 1557-1569.
55. Bortolatto, J., E. Borducchi, D. Rodriguez, A. C. Keller, E. Faquim-Mauro, K. R. Bortoluci, D. Mucida, E. Gomes, A. Christ, S. Schnyder-Candrian, et al. 2008. Toll-like receptor 4 agonists adsorbed to aluminium hydroxide adjuvant attenuate ovalbumin-specific allergic airway disease: role of MyD88 adaptor molecule and interleukin-12/interferon-γ axis. Clin. Exp. Allergy 38: 1668-1679.
56. Dillon, S., A. Agrawal, T. Van Dyke, G. Landreth, L. McCauley, A. Koh, C. Maliszewski, S. Akira, and B. Pulendran. 2004. A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J. Immunol. 172: 4733-4743. (Pubitemid 38456394)
57. h2 cell differentiation. Int. Immunol. 14: 695-700.
58. Dabbagh, K., M. E. Dahl, P. Stepick-Biek, and D. B. Lewis. 2002. Toll-like receptor 4 is required for optimal development of Th2 immune responses: role of dendritic cells. J. Immunol. 168: 4524-4530.
59. Phipps, S., C. E. Lam, G. E. Kaiko, S. Y. Foo, A. Collison, J. Mattes, J. Barry, S. Davidson, K. Oreo, L. Smith, et al. 2009. Toll/IL-1 signaling is critical for house dust mite-specific helper T cell type 2 and type 17 [corrected] responses. Am. J. Respir. Crit. Care Med. 179: 883-893.
60. Marciani, D. J. 2003. Vaccine adjuvants: role and mechanisms of action in vaccine immunogenicity. Drug Discov. Today 8: 934-943. (Pubitemid 37230013)
61. Marciani, D. J., J. B. Press, R. C. Reynolds, A. K. Pathak, V. Pathak, L. E. Gundy, J. T. Farmer, M. S. Koratich, and R. D. May. 2000. Development of semisynthetic triterpenoid saponin derivatives with immune stimulating activity. Vaccine 18: 3141-3151. (Pubitemid 30345696)
62. Marciani, D. J., R. C. Reynolds, A. K. Pathak, K. Finley-Woodman, and R. D. May. 2003. Fractionation, structural studies, and immunological characterization of the semi-synthetic Quillaja saponins derivative GPI-0100. Vaccine 21: 3961-3971. (Pubitemid 37338224)
63. + T cells. Science 327: 1098-1102.
64. Cote-Sierra, J., G. Foucras, L. Guo, L. Chiodetti, H. A. Young, J. Hu-Li, J. Zhu, and W. E. Paul. 2004. Interleukin 2 plays a central role in Th2 differentiation. Proc. Natl. Acad. Sci. USA 101: 3880-3885.
65. + T cells to generate a Th2-inducing cytokine environment. J. Exp. Med. 202: 793-804.
66. Zhu, J., J. Cote-Sierra, L. Guo, and W. E. Paul. 2003. Stat5 activation plays a critical role in Th2 differentiation. Immunity 19: 739-748.
67. Zhu, J., H. Yamane, J. Cote-Sierra, L. Guo, and W. E. Paul. 2006. GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res. 16: 3-10.
68. Sun, J., and E. J. Pearce. 2007. Suppression of early IL-4 production underlies the failure of CD4 T cells activated by TLR-stimulated dendritic cells to differentiate into Th2 cells. J. Immunol. 178: 1635-1644.
69. Crispín, J. C., and G. C. Tsokos. 2009. Transcriptional regulation of IL-2 in health and autoimmunity. Autoimmun. Rev. 8: 190-195.
70. Lan, R. Y., C. Selmi, and M. E. Gershwin. 2008. The regulatory, inflammatory, and T cell programming roles of interleukin-2 (IL-2). J. Autoimmun. 31: 7-12.
71. 3+ regulatory T cells: more of the same or a division of labor? Immunity 30: 626-635.
72. 3+ T regulatory cell-mediated suppression. Immunity 30: 636-645.
73. Rudd, C. E., A. Taylor, and H. Schneider. 2009. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol. Rev. 229: 12-26.
74. Hayashi, M., M. Kuwahara, M. Ogata, N. Miyao-Kurosaki, T. Abel, R. Ueki, M. Yano, M. Fujii, G. Hartmann, and H. Takaku. 2003. Evaluating the immune responses stimulated by CpG oligodeoxynucleotides. Nucleic Acids Res. Suppl. (3, Suppl.)323-324.
75. + T cell responses in nonhuman primates. Proc. Natl. Acad. Sci. USA 102: 15190-15194.
76. + T cell response. Immunity 25: 655-664.
77. Iweala, O. I., D. W. Smith, K. S. Matharu, I. Sada-Ovalle, D. D. Nguyen, R. H. Dekruyff, D. T. Umetsu, S. M. Behar, and C. R. Nagler. 2009. Vaccine-induced antibody isotypes are skewed by impaired CD4 T cell and invariant NKT cell effector responses in MyD88-deficient mice. J. Immunol. 183: 2252-2260.
78. + T cell priming during respiratory fungal infection. Immunity 25: 665-675.
79. Eisenbarth, S. C., A. Zhadkevich, P. Ranney, C. A. Herrick, and K. Bottomly. 2004. IL-4-dependent Th2 collateral priming to inhaled antigens independent of Toll-like receptor 4 and myeloid differentiation factor 88. J. Immunol. 172: 4527-4534. (Pubitemid 38375270)
80. Sun, J., M. Walsh, A. V. Villarino, L. Cervi, C. A. Hunter, Y. Choi, and E. J. Pearce. 2005. TLR ligands can activate dendritic cells to provide a MyD88-dependent negative signal for Th2 cell development. J. Immunol. 174: 742-751.
81. Hou, B., B. Reizis, and A. L. DeFranco. 2008. Toll-like receptors activate innate and adaptive immunity by using dendritic cell-intrinsic and -extrinsic mechanisms. Immunity 29: 272-282.
82. 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)
83. Okamura, H., H. Tsutsi, T. Komatsu, M. Yutsudo, A. Hakura, T. Tanimoto, K. Torigoe, T. Okura, Y. Nukada, K. Hattori, et al. 1995. Cloning of a new cytokine that induces IFN-γ production by T cells. Nature 378: 88-91.
84. Subramanian, G., J. W. Kazura, E. Pearlman, X. Jia, I. Malhotra, and C. L. King. 1997. B7-2 requirement for helminth-induced granuloma formation and CD4 type 2 T helper cell cytokine expression. J. Immunol. 158: 5914-5920.
85. Van Neerven, R. J., M. M. Van de Pol, J. S. Van der Zee, F. E. Stiekema, M. De Boer, and M. L. Kapsenberg. 1998. Requirement of CD28-CD86 costimulation for allergen-specific T cell proliferation and cytokine expression. Clin. Exp. Allergy 28: 808-816.
86. Schweitzer, A. N., and A. H. Sharpe. 1998. The complexity of the B7-CD28/CTLA-4 costimulatory pathway. Agents Actions Suppl. 49: 33-43.
87. De Luca, A., C. Montagnoli, T. Zelante, P. Bonifazi, S. Bozza, S. Moretti, C. D'Angelo, C. Vacca, L. Boon, F. Bistoni, et al. 2007. Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. J. Immunol. 179: 5999-6008.
88. McAleer, J. P., B. Liu, Z. Li, S. M. Ngoi, J. Dai, M. Oft, and A. T. Vella. 2010. Potent intestinal Th17 priming through peripheral lipopolysaccharide-based immunization. J. Leukoc. Biol. 88: 21-31.
89. Guo, B., E. Y. Chang, and G. Cheng. 2008. The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. J. Clin. Invest. 118: 1680-1690.
90. Mata-Haro, V., C. Cekic, M. Martin, P. M. Chilton, C. R. Casella, and T. C. Mitchell. 2007. The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4. Science 316: 1628-1632.
91. Oda, T., H. Yoshie, and K. Yamazaki. 2003. Porphyromonas gingivalis antigen preferentially stimulates T cells to express IL-17 but not receptor activator of NF-kappaB ligand in vitro. Oral Microbiol. Immunol. 18: 30-36.
92. Maitra, U., S. Davis, C. M. Reilly, and L. Li. 2009. Differential regulation of Foxp3 and IL-17 expression in CD4 T helper cells by IRAK-1. J. Immunol. 182: 5763-5769.
93. Zhang, F., G. Meng, and W. Strober. 2008. Interactions among the transcription factors Runx1, RORγt and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nat. Immunol. 9: 1297-1306.
94. H17 cell differentiation by antagonizing RORγt function. Nature 453: 236-240.
95. Zhu, J., L. Guo, B. Min, C. J. Watson, J. Hu-Li, H. A. Young, P. N. Tsichlis, and W. E. Paul. 2002. Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation. Immunity 16: 733-744.
96. h17 differentiation by inhibiting RORγt activity. Int. Immunol. 21: 881-889.
97. Kamon, H., T. Kawabe, H. Kitamura, J. Lee, D. Kamimura, T. Kaisho, S. Akira, A. Iwamatsu, H. Koga, M. Murakami, and T. Hirano. 2006. TRIF-GEFH1-RhoB pathway is involved in MHCII expression on dendritic cells that is critical for CD4 T-cell activation. EMBO J. 25: 4108-4119. (Pubitemid 44338751)