The IL-12 family of cytokines in infection, inflammation and autoimmune disorders

Inflammation and Allergy - Drug Targets

Volumn 8, Issue 1, 2009, Pages 40-52

  Gee, Katrina ^a   Guzzo, Christina ^a   Mat, Nor Fazila Che ^a   Ma, Wei ^b   Kumar, Ashok ^b  

^a QUEEN S UNIVERSITY   (Canada)

^b UNIVERSITY OF OTTAWA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; INTERLEUKIN 12; INTERLEUKIN 23; INTERLEUKIN 27; INTERLEUKIN 35; UNCLASSIFIED DRUG;

ALLERGIC ENCEPHALOMYELITIS; ANTIANGIOGENIC ACTIVITY; ARTHRITIS; AUTOIMMUNE DISEASE; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; BACTERIAL INFECTION; COLITIS; CROHN DISEASE; DENDRITIC CELL; HUMAN; IMMUNOPATHOGENESIS; IMMUNOREGULATION; INFECTION; INFLAMMATION; INNATE IMMUNITY; LUPUS VULGARIS; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE PROLIFERATION; MACROPHAGE; MONOCYTE; MULTIPLE SCLEROSIS; NATURAL KILLER CELL; NEOPLASM; NONHUMAN; PARASITOSIS; PSORIASIS; REVIEW; SIGNAL TRANSDUCTION; TH1 CELL; TH17 CELL;

ANIMALS; AUTOIMMUNE DISEASES; CANCER VACCINES; HUMANS; IMMUNITY, CELLULAR; INFECTION; INFLAMMATION; INTERLEUKIN-12; INTERLEUKIN-23; INTERLEUKINS; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; T-LYMPHOCYTE SUBSETS; TH1 CELLS;

EID: 69749101475     PISSN: 18715281     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152809787582507     Document Type: Review

References (188)

1. Beadling, C.; Slifka, M.K. Regulation of innate and adaptive immune responses by the related cytokines IL-12, IL-23, and IL-27. Arch. Immunol. Ther. Exp. (Warsz), 2006, 54, 15-24.
2. Hunter, C.A. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat. Rev. Immunol., 2005, 5, 521-531.
3. Oppmann, B.; Lesley, R.; Blom, B.; Timans, J.C.; Xu, Y.; Hunte, B.; Vega, F.; Yu, N.; Wang, J.; Singh, K.; Zonin, F.; Vaisberg, E.; Churakova, T.; Liu, M.; Gorman, D.; Wagner, J.; Zurawski, S.; Liu, Y.; Abrams, J.S.; Moore, K.W.; Rennick, D.; Waal-Malefyt, R. Hannum C, Bazan JF, Kastelein RA. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity, 2000, 13, 715-725.
4. Parham, C.; Chirica, M.; Timans, J.; Vaisberg, E.; Travis, M.; Cheung, J.; Pflanz, S.; Zhang, R.; Singh, K. P.; Vega, F.; To, W.; Wagner, J.; O'Farrell, A.M.; McClanahan, T.; Zurawski, S.; Hannum, C.; Gorman, D.; Rennick, D.M.; Kastelein, R.A.; de Waal, M.R.; Moore, K.W. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J. Immunol., 2002, 168, 5699-5708.
5. Batten, M.; Ghilardi, N. The biology and therapeutic potential of interleukin 27. J. Mol. Med., 2007, 85, 661-672.
6. Kastelein, R.A.; Hunter, C.A.; Cua, D.J. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu. Rev. Immunol., 2007, 25, 221-242.
7. Villarino, A.V.; Huang, E.; Hunter, C.A. Understanding the pro- and anti-inflammatory properties of IL-27. J. Immunol., 2004, 173, 715-720.
8. Pflanz, S.; Timans, J.C.; Cheung, J.; Rosales, R.; Kanzler, H.; Gilbert, J.; Hibbert, L.; Churakova, T.; Travis, M.; Vaisberg, E.; Blumenschein, W.M.; Mattson, J.D.; Wagner, J.L.; To, W.; Zurawski, S.; McClanahan, T.K.; Gorman, D.M.; Bazan, J.F.; De Waal, M.R.; Rennick, D.; Kastelein, R.A. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity, 2002, 16, 779-790.
9. Niedobitek, G.; Pazolt, D.; Teichmann, M.; Devergne, O. Frequent expression of the Epstein-Barr virus (EBV)-induced gene, EBI3, an IL-12 p40-related cytokine, in Hodgkin and Reed-Sternberg cells. J. Pathol., 2002, 198, 310-316.
10. Pirhonen, J.; Siren, J.; Julkunen, I.; Matikainen, S. IFN-alpha regulates Toll-like receptor-mediated IL-27 gene expression in human macrophages. J. Leukoc. Biol., 2007, 82, 1185-1192.
11. Bardel, E.; Larousserie, F.; Charlot-Rabiega, P.; Coulomb-L'Hermine, A.; Devergne, O. Human CD4+ CD25+ Foxp3+ regulatory T cells do not constitutively express IL-35. J. Immunol., 2008, 181, 6898-6905.
12. Goriely, S.; Goldman, M. Interleukin-12 family members and the balance between rejection and tolerance. Curr. Opin. Organ Transplant., 2008, 13, 4-9.
13. Yang, J.; Yang, M.; Htut, T.M.; Ouyang, X.; Hanidu, A.; Li, X.; Sellati, R.; Jiang, H.; Zhang, S.; Li, H.; Zhao, J.; Ting, A.T.; Mayer, L.; Unkeless, J.C.; Labadia, M.E.; Hodge, M.; Li, J.; Xiong, H. Epstein-Barr virus-induced gene 3 negatively regulates IL-17, IL-22 and RORgamma t. Eur. J. Immunol., 2008, 38, 1204-1214.
14. Collison, L.W.; Workman, C.J.; Kuo, T.T.; Boyd, K.; Wang, Y.; Vignali, K.M.; Cross, R.; Sehy, D.; Blumberg, R.S.; Vignali, D.A. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature, 2007, 450, 566-569.
15. Niedbala, W.; Wei, X.Q.; Cai, B.; Hueber, A.J.; Leung, B.P.; McInnes, I.B.; Liew, F. Y. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur. J. Immunol., 2007, 37, 3021-3029.
16. Gately, M.K.; Renzetti, L.M.; Magram, J.; Stern, A.S.; Adorini, L.; Gubler, U.; Presky, D.H. The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu. Rev. Immunol., 1998, 16, 495-521.
17. Ma, X.; Trinchieri, G. Regulation of interleukin-12 production in antigen-presenting cells. Adv. Immunol., 2001, 79, 55-92.
18. Sieburth, D.; Jabs, E.W.; Warrington, J.A.; Li, X.; Lasota, J.; La-Forgia, S.; Kelleher, K.; Huebner, K.; Wasmuth, J.J.; Wolf, S.F. Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5. Genomics, 1992, 14, 59-62.
19. Merberg, D.M.; Wolf, S.F.; Clark, S.C. Sequence similarity between NKSF and the IL-6/G-CSF family. Immunol. Today, 1992, 13, 77-78.
20. Gearing, D.P.; Cosman, D. Homology of the p40 subunit of natural killer cell stimulatory factor (NKSF) with the extracellular domain of the interleukin-6 receptor. Cell, 1991, 66, 9-10.
21. Gillessen, S.; Carvajal, D.; Ling, P.; Podlaski, F.J.; Stremlo, D.L.; Familletti, P.C.; Gubler, U.; Presky, D.H.; Stern, A.S.; Gately, M.K. Mouse interleukin-12 (IL-12) p40 homodimer: a potent IL-12 antagonist. Eur. J. Immunol., 1995, 25, 200-206.
22. Podlaski, F.J.; Nanduri, V.B.; Hulmes, J.D.; Pan, Y.C.; Levin, W.; Danho, W.; Chizzonite, R.; Gately, M.K.; Stern, A. S. Molecular characterization of interleukin 12. Arch. Biochem. Biophys, 1992, 294, 230-237.
23. Ling, P.; Gately, M.K.; Gubler, U.; Stern, A.S.; Lin, P.; Hollfelder, K.; Su, C.; Pan, Y. C.; Hakimi, J. Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity. J. Immunol., 1995, 154, 116-127.
24. Piccotti, J.R.; Chan, S.Y.; Goodman, R.E.; Magram, J.; Eichwald, E.J.; Bishop, D.K. IL-12 antagonism induces T helper 2 responses, yet exacerbates cardiac allograft rejection. Evidence against a dominant protective role for T helper 2 cytokines in alloimmunity. J. Immunol., 1996, 157, 1951-1957.
25. Naeger, L.K.; McKinney, J.; Salvekar, A.; Hoey, T. Identification of a STAT4 binding site in the interleukin-12 receptor required for signalling. J. Biol. Chem., 1999, 274, 1875-1878.
26. Jones, D.; Elloso, M.M.; Showe, L.; Williams, D.; Trinchieri, G.; Scott, P. Differential regulation of the interleukin-12 receptor during the innate immune response to Leishmania major. Infect. Immun., 1998, 66, 3818-3824.
27. Wu, C.Y.; Gadina, M.; Wang, K.; O'Shea, J.; Seder, R.A. Cytokine regulation of IL-12 receptor beta2 expression: differential effects on human T and NK cells. Eur. J. Immunol., 2000, 30, 1364-1374.
28. Zhang, G.X.; Yu, S.; Gran, B.; Li, J.; Siglienti, I.; Chen, X.; Calida, D.; Ventura, E.; Kamoun, M.; Rostami, A. Role of IL-12 receptor beta 1 in regulation of T cell response by APC in experimental autoimmune encephalomyelitis. J. Immunol., 2003, 171, 4485-4492.
29. Bacon, C.M.; McVicar, D.W.; Ortaldo, J.R.; Rees, R.C.; O'Shea, J.J.; Johnston, J.A. Interleukin 12 (IL-12) induces tyrosine phosphorylation of JAK2 and TYK2: differential use of Janus family tyrosine kinases by IL-2 and IL-12. J. Exp. Med., 1995, 181, 399-404.
30. Gollob, J.A.; Murphy, E.A.; Mahajan, S.; Schnipper, C.P.; Ritz, J.; Frank, D.A. Altered interleukin-12 responsiveness in Th1 and Th2 cells is associated with the differential activation of STAT5 and STAT1. Blood, 1998, 91, 1341-1354.
31. Ozbek, N.; Fieschi, C.; Yilmaz, B.T.; de, B.L.; Demirhan, B.; Feinberg, J.; Bikmaz, Y. E.; Casanova, J.L. Interleukin-12 receptor beta 1 chain deficiency in a child with disseminated tuberculosis. Clin. Infect. Dis., 2005, 40, e55-e58.
32. Mikus, L.D.; Rosenthal, L.A.; Sorkness, R.L.; Lemanske, R.F. Jr. Reduced interferon-gamma secretion by natural killer cells from rats susceptible to postviral chronic airway dysfunction. Am. J. Respir. Cell Mol. Biol., 2001, 24, 74-82.
33. Hsieh, C.S.; Macatonia, S.E.; Tripp, C.S.; Wolf, S.F.; O'Garra, A.; Murphy, K.M. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science, 1993, 260, 547-549.
34. Seder, R.A.; Gazzinelli, R.; Sher, A.; Paul, W.E. Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc. Natl. Acad. Sci. USA, 1993, 90, 10188-10192.
35. Murphy, E.E.; Terres, G.; Macatonia, S.E.; Hsieh, C.S.; Mattson, J.; Lanier, L.; Wysocka, M.; Trinchieri, G.; Murphy, K.; O'Garra, A. B7 and interleukin 12 cooperate for proliferation and interferon gamma production by mouse T helper clones that are unresponsive to B7 costimulation. J. Exp. Med., 1994, 180, 223-231.
36. Tominaga, K.; Yoshimoto, T.; Torigoe, K.; Kurimoto, M.; Matsui, K.; Hada, T.; Okamura, H.; Nakanishi, K. IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells. Int. Immunol., 2000, 12, 151-160.
37. Yu, C.R.; Lin, J.X.; Fink, D.W.; Akira, S.; Bloom, E.T.; Yamauchi, A. Differential utilization of Janus kinase-signal transducer activator of transcription signalling pathways in the stimulation of human natural killer cells by IL-2, IL-12, and IFN-alpha. J. Immunol., 1996, 157, 126-137.
38. Allavena, P.; Paganin, C.; Zhou, D.; Bianchi, G.; Sozzani, S.; Mantovani, A. Interleukin-12 is chemotactic for natural killer cells and stimulates their interaction with vascular endothelium. Blood, 1994, 84, 2261-2268.
39. Airoldi, I.; Gri, G.; Marshall, J.D.; Corcione, A.; Facchetti, P.; Guglielmino, R.; Trinchieri, G.; Pistoia, V. Expression and function of IL-12 and IL-18 receptors on human tonsillar B cells. J. Immunol., 2000, 165, 6880-6888.
40. Otani, T.; Nakamura, S.; Toki, M.; Motoda, R.; Kurimoto, M.; Orita, K. Identification of IFN-gamma-producing cells in IL-12/IL-18-treated mice. Cell Immunol., 1999, 198, 111-119.
41. Yoshimoto, T.; Okamura, H.; Tagawa, Y.I.; Iwakura, Y.; Nakanishi, K. Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells. Proc. Natl. Acad. Sci. USA, 1997, 94, 3948-3953.
42. Moser, M.; Murphy, K.M. Dendritic cell regulation of TH1-TH2 development. Nat. Immunol., 2000, 1, 199-205.
43. Dalton, D.K.; Pitts-Meek, S.; Keshav, S.; Figari, I.S.; Bradley, A.; Stewart, T.A. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science, 1993, 259, 1739-1742.
44. Kennedy, M.K.; Picha, K.S.; Fanslow, W.C.; Grabstein, K.H.; Alderson, M.R.; Clifford, K.N.; Chin, W.A.; Mohler, K.M. CD40/CD40 ligand interactions are required for T cell-dependent production of interleukin-12 by mouse macrophages. Eur. J. Immunol., 1996, 26, 370-378.
45. Lederer, J.A.; Perez, V.L.; DesRoches, L.; Kim, S.M.; Abbas, A.K.; Lichtman, A.H. Cytokine transcriptional events during helper T cell subset differentiation. J. Exp. Med., 1996, 184, 397-406.
46. Reiner, S.L.; Zheng, S.; Wang, Z.E.; Stowring, L.; Locksley, R.M. Leishmania promastigotes evade interleukin 12 (IL-12) induction by macrophages and stimulate a broad range of cytokines from CD4+ T cells during initiation of infection. J. Exp. Med., 1994, 179, 447-456.
47. Liu, J.; Cao, S.; Herman, L.M.; Ma, X. Differential regulation of interleukin (IL)-12 p35 and p40 gene expression and interferon (IFN-)-gamma-primed IL-12 production by IFN regulatory factor 1. J. Exp. Med., 2003, 198, 1265-1276.
48. Ma, X.; Gri, G.; Trinchieri, G. A novel ets-2-related nuclear factor is involved in transcriptional activation of the human interleukin-12 p40 gene promoter in response to interferon-gamma and LPS stimulation of monocytic cells. Ann. N.Y. Acad. Sci., 1996, 795, 357-360.
49. Maruyama, S.; Sumita, K.; Shen, H.; Kanoh, M.; Xu, X.; Sato, M.; Matsumoto, M.; Shinomiya, H.; Asano, Y. Identification of IFN regulatory factor-1 binding site in IL-12 p40 gene promoter. J. Immunol., 2003, 170, 997-1001.
50. Masumi, A.; Tamaoki, S.; Wang, I.M.; Ozato, K.; Komuro, K. IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages. FEBS Lett., 2002, 531, 348-353.
51. Goriely, S.; Molle, C.; Nguyen, M.; Albarani, V.; Haddou, N.O.; Lin, R.; De, W.D.; Flamand, V.; Willems, F.; Goldman, M. Interferon regulatory factor 3 is involved in Toll-like receptor 4 (TLR4)-and TLR3-induced IL-12p35 gene activation. Blood, 2006, 107, 1078-1084.
52. D'Andrea, A.; ste-Amezaga, M.; Valiante, N.M.; Ma, X.; Kubin, M.; Trinchieri G. Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J. Exp. Med., 1993, 178, 1041-1048.
53. ste-Amezaga, M.; Ma, X.; Sartori, A.; Trinchieri G. Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10. J. Immunol., 1998, 160, 5936-5944.
54. Driessler, F.; Venstrom, K.; Sabat, R.; Asadullah, K.; Schottelius, A. J. Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappaB activity: a role for p50. Clin. Exp. Immunol., 2004, 135, 64-73.
55. Rahim, S.S.; Khan, N.; Boddupalli, C.S.; Hasnain, S.E.; Mukhopadhyay, S. Interleukin-10 (IL-10) mediated suppression of IL-12 production in RAW 264.7 cells also involves c-rel transcription factor. Immunology, 2005, 114, 313-321.
56. Zhou, L.; Nazarian, A.A.; Smale, S.T. Interleukin-10 inhibits interleukin-12 p40 gene transcription by targeting a late event in the activation pathway. Mol. Cell Biol., 2004, 24, 2385-2396.
57. Berg, D. J.; Kuhn, R.; Rajewsky, K.; Muller, W.; Menon, S.; Davidson, N.; Grunig, G.; Rennick, D. Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance. J. Clin. Invest., 1995, 96, 2339-2347.
58. Gazzinelli, R.T.; Wysocka, M.; Hieny, S.; Scharton-Kersten, T.; Cheever, A.; Kuhn, R.; Muller, W.; Trinchieri, G.; Sher, A. In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. J. Immunol., 1996, 157, 798-805.
59. Branton, M.H.; Kopp, J.B. TGF-beta and fibrosis. Microbes Infect., 1999, 1, 1349-1365.
60. McRae, B.L.; Beilfuss, B.A.; van Seventer, G.A. IFN-beta differentially regulates CD40-induced cytokine secretion by human dendritic cells. J. Immunol., 2000, 164, 23-28.
61. Cousens, L.P.; Orange, J.S.; Su, H.C.; Biron, C.A. Interferonalpha/beta inhibition of interleukin 12 and interferon-gamma production in vitro and endogenously during viral infection. Proc. Natl. Acad. Sci. USA, 1997, 94, 634-639.
62. Karp, C.L.; Wysocka, M.; Wahl, L.M.; Ahearn, J.M.; Cuomo, P.J.; Sherry, B.; Trinchieri, G.; Griffin, D.E. Mechanism of suppression of cell-mediated immunity by measles virus. Science, 1996, 273, 228-231.
63. Oppmann, B.; Lesley, R.; Blom, B.; Timans, J.C.; Xu, Y.; Hunte, B.; Vega, F.; Yu, N.; Wang, J.; Singh, K.; Zonin, F.; Vaisberg, E.; Churakova, T.; Liu, M.; Gorman, D.; Wagner, J.; Zurawski, S.; Liu, Y.; Abrams, J.S.; Moore, K.W.; Rennick, D.; de Waal-Malefyt, R.; Hannum, C.; Bazan, J.F.; Kastelein, R.A. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity, 2000, 13, 715-725.
64. Presky, D.H.; Yang, H.; Minetti, L.J.; Chua, A.O.; Nabavi, N.; Wu, C.Y.; Gately, M. K.; Gubler, U. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc. Natl. Acad. Sci. USA, 1996, 93, 14002-14007.
65. Desai, B.B.; Quinn, P.M.; Wolitzky, A.G.; Mongini, P.K.; Chizzonite, R.; Gately, M. K. IL-12 receptor. II. Distribution and regulation of receptor expression. J. Immunol., 1992, 148, 3125-3132.
66. Belladonna, M.L.; Renauld, J.C.; Bianchi, R.; Vacca, C.; Fallarino, F.; Orabona, C.; Fioretti, M.C.; Grohmann, U.; Puccetti, P. IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells. J. Immunol., 2002, 168, 5448-5454.
67. Aggarwal, S.; Ghilardi, N.; Xie, M.H.; de Sauvage, F.J.; Gurney, A.L. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J. Biol. Chem., 2003, 278, 1910-1914.
68. Tokumasa, N.; Suto, A.; Kagami, S.; Furuta, S.; Hirose, K.; Watanabe, N.; Saito, Y.; Shimoda, K.; Iwamoto, I.; Nakajima, H. Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-gamma production and the induction of Th1 cell differentiation. Blood, 2007, 110, 553-560.
69. Lankford, C.S.; Frucht, D.M. A unique role for IL-23 in promoting cellular immunity. J. Leukoc. Biol., 2003, 73, 49-56.
70. Minegishi, Y.; Saito, M.; Morio, T.; Watanabe, K.; Agematsu, K.; Tsuchiya, S.; Takada, H.; Hara, T.; Kawamura, N.; Ariga, T.; Kaneko, H.; Kondo, N.; Tsuge, I.; Yachie, A.; Sakiyama, Y.; Iwata, T.; Bessho, F.; Ohishi, T.; Joh, K.; Imai, K.; Kogawa, K.; Shinohara, M.; Fujieda, M.; Wakiguchi, H.; Pasic, S.; Abinun, M.; Ochs, H.D.; Renner, E.D.; Jansson, A.; Belohradsky, B.H.; Metin, A.; Shimizu, N.; Mizutani, S.; Miyawaki, T.; Nonoyama, S.; Karasuyama, H. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity, 2006, 25, 745-755.
71. Yang, X.O.; Panopoulos, A.D.; Nurieva, R.; Chang, S.H.; Wang, D.; Watowich, S.S.; Dong, C. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J. Biol. Chem., 2007, 282, 9358-9363.
72. Mathur, A.N.; Chang, H.C.; Zisoulis, D.G.; Stritesky, G.L.; Yu, Q.; O'Malley, J.T.; Kapur, R.; Levy, D.E.; Kansas, G.S.; Kaplan, M.H. Stat3 and Stat4 direct development of IL-17-secreting Th cells. J. Immunol., 2007, 178, 4901-4907.
73. McKenzie, B.S.; Kastelein, R.A.; Cua, D.J. Understanding the IL-23-IL-17 immune pathway. Trends Immunol., 2006, 27, 17-23.
74. Chen, Y.; Langrish, C.L.; McKenzie, B.; Joyce-Shaikh, B.; Stumhofer, J.S.; McClanahan, T.; Blumenschein, W.; Churakovsa, T.; Low, J.; Presta, L.; Hunter, C.A.; Kastelein, R.A.; Cua, D.J. Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J. Clin. Invest., 2006, 116, 1317-1326.
75. Ye, P.; Rodriguez, F.H.; Kanaly, S.; Stocking, K.L.; Schurr, J.; Schwarzenberger, P.; Oliver, P.; Huang, W.; Zhang, P.; Zhang, J.; Shellito, J.E.; Bagby, G.J.; Nelson, S.; Charrier, K.; Peschon, J.J.; Kolls, J.K. Requirement of interleukin 17 receptor signalling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med., 2001, 20, 194, 519-527.
76. Happel, K.I.; Zheng, M.; Young, E.; Quinton, L.J.; Lockhart, E.; Ramsay, A.J.; Shellito, J.E.; Schurr, J.R.; Bagby, G.J.; Nelson, S.; Kolls, J.K. Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection. J. Immunol., 2003, 170, 4432-4436.
77. Cooper, A.M.; Magram, J.; Ferrante, J.; Orme, I.M. Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with Mycobacterium tuberculosis. J. Exp. Med., 1997, 186, 39-45.
78. Muller, U.; Kohler, G.; Mossmann, H.; Schaub, G.A.; Alber, G.; Di Santo, J.P.; Brombacher, F.; Holscher, C. IL-12-independent IFN-gamma production by T cells in experimental Chagas' disease is mediated by IL-18. J. Immunol., 2001, 167, 3346-3353.
79. Mattner, F.; Magram, J.; Ferrante, J.; Launois, P.; Di, P.K.; Behin, R.; Gately, M.K.; Louis, J.A.; Alber, G. Genetically resistant mice lacking interleukin-12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response. Eur. J. Immunol., 1996, 26, 1553-1559.
80. Wu, C.; Wang, X.; Gadina, M.; O'Shea, J.J.; Presky, D.H.; Magram, J. IL-12 receptor beta 2 (IL-12R beta 2)-deficient mice are defective in IL-12-mediated signalling despite the presence of high affinity IL-12 binding sites. J. Immunol., 2000, 165, 6221-6228.
81. Altare, F.; Durandy, A.; Lammas, D.; Emile, J.F.; Lamhamedi, S.; Le, D.F.; Drysdale, P.; Jouanguy, E.; Doffinger, R.; Bernaudin, F.; Jeppsson, O.; Gollob, J.A.; Meinl, E.; Segal, A.W.; Fischer, A.; Kumararatne, D.; Casanova, J.L. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science, 1998, 280, 1432-1435.
82. Goriely, S.; Goldman, M. The interleukin-12 family: new players in transplantation immunity? Am. J. Transplant, 2007, 7, 278-284.
83. Orange, J.S.; Wolf, S.F.; Biron, C.A. Effects of IL-12 on the response and susceptibility to experimental viral infections. J. Immunol., 1994, 152, 1253-1264.
84. Karp, C.L.; Wysocka, M.; Wahl, L.M.; Ahearn, J.M.; Cuomo, P.J.; Sherry, B.; Trinchieri, G.; Griffin, D.E. Mechanism of suppression of cell-mediated immunity by measles virus. Science, 1996, 273, 228-231.
85. Cavanaugh, V.J.; Guidotti, L.G.; Chisari, F.V. Interleukin-12 inhibits hepatitis B virus replication in transgenic mice. J. Virol., 1997, 71, 3236-3243.
86. Carr, J.A.; Rogerson, J.; Mulqueen, M.J.; Roberts, N.A.; Booth, R.F. Interleukin-12 exhibits potent antiviral activity in experimental herpesvirus infections. J. Virol., 1997, 71, 7799-7803.
87. Chehimi, J.; Starr, S.E. Frank, I.; D'Andrea, A.; Ma, X.; MacGregor, R.R.; Sennelier, J.; Trinchieri, G. Impaired interleukin 12 production in human immunodeficiency virus-infected patients. J. Exp. Med., 1994, 179, 1361-1366.
88. Romani, L.; Puccetti, P.; Bistoni, F. Interleukin-12 in infectious diseases. Clin. Microbiol. Rev., 1997, 10, 611-636.
89. Ansari, A.A.; Mayne, A.E.; Sundstrom, J.B.; Bostik, P.; Gri mm, B.; Altman, J.D.; Villinger, F. Administration of recombinant rhesus interleukin-12 during acute simian immunodeficiency virus (SIV) infection leads to decreased viral loads associated with prolonged survival in SIVmac251-infected rhesus macaques. J. Virol., 2002, 76, 1731-1743.
90. Little, R.F.; Pluda, J.M.; Wyvill, K.M.; Rodriguez-Chavez, I.R.; Tosato, G.; Catanzaro, A.T.; Steinberg, S.M.; Yarchoan, R. Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Blood, 2006, 107, 4650-4657.
91. Jacobson, M.A.; Spritzler, J.; Landay, A.; Chan, E.; Katzenstein, D.; Schock, B.; Fox, L.; Roe, J.; Kundu, S.; Pollard, R. A Phase I, placebo-controlled trial of multi-dose recombinant human interleukin-12 in patients with HIV infection. [I AIDS I], 2002, 16, 1147-1154.
92. Wiekowski, M.T.; Leach, M.W.; Evans, E.W.; Sullivan, L.; Chen, S.C.; Vassileva, G.; Bazan, J.F.; Gorman, D.M.; Kastelein, R.A.; Narula, S.; Lira, S.A. Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death. J. Immunol., 2001, 166, 7563-7570.
93. Cua, D.J.; Sherlock, J.; Chen, Y. Murphy, C.A.; Joyce, B.; Seymour, B.; Lucian, L.; To, W.; Kwan, S.; Churakova, T.; Zurawski, S.; Wiekowski, M.; Lira, S.A.; Gorman, D.; Kastelein, R.A.; Sedgwick, J.D. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature, 2003, 421, 744-748.
94. Ghilardi, N.; Kljavin, N.; Chen, Q.; Lucas, S.; Gurney, A.L.; de Sauvage, F.J. Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice. J. Immunol., 2004, 172, 2827-2833.
95. Gran, B.; Zhang, G.X.; Yu, S.; Li, J.; Chen, X.H.; Ventura, E S.; Kamoun, M.; Rostami, A. IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J. Immunol., 2002, 169, 7104-7110.
96. Becher, B.; Durell, B.G.; Noelle, R.J. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J. Clin. Invest., 2002, 110, 493-497.
97. Langrish, C.L.; Chen, Y.; Blumenschein, W.M.; Mattson, J.; Basham, B.; Sedgwick, J. D.; McClanahan, T.; Kastelein, R.A.; Cua, D.J. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med., 2005, 201, 233-240.
98. Murphy, C.A.; Langrish, C.L.; Chen, Y.; Blumenschein, W.; McClanahan, T.; Kastelein, R.A.; Sedgwick, J.D.; Cua, D.J. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp. Med., 2003, 198, 1951-1957.
99. Krakauer, M.; Sorensen, P.; Khademi, M.; Olsson, T.; Sellebjerg, F. Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis: interferon-{beta} treatment increases IL-10 mRNA expression while reducing IL-23 mRNA expression. Mult. Scler., 2008, 14, 622-630.
100. Chen, X.; Tan, Z.; Yue, Q.; Liu, H.; Liu, Z.; Li, J. The expression of interleukin-23 (p19/p40) and inteleukin-12 (p35/p40) in psoriasis skin. J. Huazhong Univ. Sci. Technolog. Med. Sci., 2006, 26, 750-752.
101. Lee, E.; Trepicchio, W.L.; Oestreicher, J.L.; Pittman, D.; Wang, F.; Chamian, F.; Dhodapkar, M.; Krueger, J. G. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J. Exp. Med., 2004, 199, 125-130.
102. Li, J.; Chen, X.; Liu, Z.; Yue, Q.; Liu, H. Expression of Th17 cytokines in skin lesions of patients with psoriasis. J. Huazhong. Univ. Sci. Technolog. Med. Sci., 2007, 27, 330-332.
103. Chan, J.R.; Blumenschein, W.; Murphy, E.; Diveu, C.; Wiekowski, M.; Abbondanzo, S.; Lucian, L.; Geissler, R.; Brodie, S.; Kimball, A.B.; Gorman, D.M.; Smith, K.; de Waal, M.R.; Kastelein, R.A.; McClanahan, T.K.; Bowman, E.P. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J. Exp. Med., 2006, 203, 2577-2587.
104. Toichi, E.; Torres, G.; McCormick, T.S.; Chang, T.; Mascelli, M.A.; Kauffman, C.L.; Aria, N.; Gottlieb, A.B.; Everitt, D.E.; Frederick, B.; Pendley, C.E.; Cooper, K.D. An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL-12/IL-23 in psoriasis. J. Immunol., 2006, 177, 4917-4926.
105. Krueger, G.G.; Langley, R.G.; Leonardi, C.; Yeilding, N.; Guzzo, C.; Wang, Y.; Dooley, L.T.; Lebwohl, M. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N. Engl. J. Med., 2007, 356, 580-592.
106. Kauffman, C.L.; Aria, N.; Toichi, E.; McCormick, T.S.; Cooper, K.D.; Gottlieb, A.B.; Everitt, D.E.; Frederick, B.; Zhu, Y.; Graham, M.A.; Pendley, C. E.; Mascelli, M.A. A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis. J. Invest. Dermatol., 2004, 123, 1037-1044.
107. Gottlieb, A.B.; Cooper, K.D.; McCormick, T.S.; Toichi, E.; Everitt, D.E.; Frederick, B.; Zhu, Y.; Pendley, C.E.; Graham, M.A.; Mascelli, M.A. A phase 1, double-blind, placebo-controlled study evaluating single subcutaneous administrations of a human interleukin-12/23 monoclonal antibody in subjects with plaque psoriasis. Curr. Med. Res. Opin., 2007, 23, 1081-1092.
108. Reddy, M.; Davis, C.; Wong, J.; Marsters, P.; Pendley, C.; Prabhakar, U. Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275. Cell Immunol., 2007, 247, 1-11.
109. Ding, C.; Xu, J.; Li, J. ABT-874, a fully human monoclonal anti-IL-12/ IL-23 antibody for the potential treatment of autoimmune diseases. Curr. Opin. Investig. Drugs, 2008, 9, 515-522.
110. Garcia, V.E.; Chang, M.; Brandon, R.; Li, Y.; Matsunami, N.; Callis-Duffin, K.P.; Civello, D.; Rowland, C.M.; Bui, N.; Catanese, J.J.; Krueger, G.G.; Leppert, M.F.; Begovich, A.B.; Schrodi, S.J. Detailed genetic characterization of the interleukin-23 receptor in psoriasis. Genes Immun., 2008, 9, 546-555.
111. Schmidt, C.; Giese, T.; Ludwig, B.; Mueller-Molaian, I.; Marth, T.; Zeuzem, S.; Meuer, S.C.; Stallmach, A. Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis. Inflamm. Bowel Dis., 2005, 11, 16-23.
112. Fuss, I.J.; Becker, C.; Yang, Z.; Groden, C.; Hornung, R.L.; Heller, F.; Neurath, M.F.; Strober, W.; Mannon, P.J. Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody. Inflamm. Bowel Dis., 2006, 12, 9-15.
113. Kamada, N.; Hisamatsu, T.; Okamoto, S.; Sato, T.; Matsuoka, K.; Arai, K.; Nakai, T.; Hasegawa, A.; Inoue, N.; Watanabe, N.; Akagawa, K.S.; Hibi, T. Abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess production of IL-12 and IL-23 in response to bacteria. J. Immunol., 2005, 175, 6900-6908.
114. Yen, D.; Cheung, J.; Scheerens, H.; Poulet, F.; McClanahan, T.; McKenzie, B.; Kleinschek, M.A.; Owyang, A.; Mattson, J.; Blumenschein, W.; Murphy, E.; Sathe, M.; Cua, D.J.; Kastelein, R.A.; Rennick, D. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J. Clin. Invest., 2006, 116, 1310-1316.
115. Kamada, N.; Hisamatsu, T.; Okamoto, S.; Chinen, H.; Kobayashi, T.; Sato, T.; Sakuraba, A.; Kitazume, M.T.; Sugita, A.; Koganei, K.; Akagawa, K.S.; Hibi, T. Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. J. Clin. Invest., 2008, 118, 2269-2280.
116. Becker, C.; Dornhoff, H.; Neufert, C.; Fantini, M. C.; Wirtz, S.; Huebner, S.; Nikolaev, A.; Lehr, H.A.; Murphy, A.J.; Valenzuela, D.M.; Yancopoulos, G.D.; Galle, P.R.; Karow, M.; Neurath, M.F. Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J. Immunol., 2006, 177, 2760-2764.
117. Kullberg, M.C.; Jankovic, D.; Feng, C.G.; Hue, S.; Gorelick, P.L.; McKenzie, B.S.; Cua, D.J.; Powrie, F.; Cheever, A.W.; Maloy, K.J.; Sher, A. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J. Exp. Med., 2006, 203, 2485-2494.
118. Duerr, R.H.; Taylor, K.D.; Brant, S.R.; Rioux, J.D.; Silverberg, M.S.; Daly, M.J.; Steinhart, A.H.; Abraham, C.; Regueiro, M.; Griffiths, A.; Dassopoulos, T.; Bitton, A.; Yang, H.; Targan, S.; Datta, L.W.; Kistner, E.O.; Schumm, L.P.; Lee, A.T.; Gregersen, P.K.; Barmada, M.M.; Rotter, J.I.; Nicolae, D.L.; Cho, H. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science, 2006, 314, 1461-1463.
119. Sheibanie, A.F.; Tadmori, I.; Jing, H.; Vassiliou, E.; Ganea, D. Prostaglandin E2 induces IL-23 production in bone marrow-derived dendritic cells. FASEB J., 2004, 18, 1318-1320.
120. Sheibanie, A.F.; Yen, J.H.; Khayrullina, T.; Emig, F.; Zhang, M.; Tuma, R.; Ganea, D. The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23-->IL-17 axis. J. Immunol., 2007, 178, 8138-8147.
121. Pang, Y.H.; Zheng, C.Q.; Yang, X.Z.; Zhang, W.J. Increased expression and activation of IL-12-induced Stat4 signalling in the mucosa of ulcerative colitis patients. Cell Immunol., 2007, 248, 115-120.
122. Fukata, M.; Breglio, K.; Chen, A.; Vamadevan, A.S.; Goo, T.; Hsu, D.; Conduah, D.; Xu, R.; Abreu, M.T. The myeloid differentiation factor 88 (MyD88) is required for CD4+ T cell effector function in a murine model of inflammatory bowel disease. J. Immunol., 2008, 180, 1886-1894.
123. Elson, C.O.; Cong, Y.; Weaver, C.T.; Schoeb, T.R.; McClanahan, T.K.; Fick, R.B.; Kastelein, R.A. Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology, 2007, 132, 2359-2370.
124. Liu, Z.; Jiu, J.; Liu, S.; Fa, X.; Li, F.; Du, Y. Blockage of tumour necrosis factor prevents intestinal mucosal inflammation through down-regulation of interleukin-23 secretion. J. Autoimmun., 2007, 29, 187-194.
125. Izcue, A.; Hue, S.; Buonocore, S.; Arancibia-Carcamo, C.V.; Ahern, P.P.; Iwakura, Y.; Maloy, K.J.; Powrie, F. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity, 2008, 28, 559-570.
126. Pflanz, S.; Hibbert, L.; Mattson, J.; Rosales, R.; Vaisberg, E.; Bazan, J. F.; Phillips, J. H.; McClanahan, T.K.; de Waal, M.R.; Kastelein, R.A. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J. Immunol., 2004, 172, 2225-2231.
127. Chen, Q.; Ghilardi, N.; Wang, H.; Baker, T.; Xie, M.H.; Gurney, A.; Grewal, I.S.; De Sauvage, F.J. Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature, 2000, 407, 916-920.
128. Sprecher, C.A.; Grant, F.J.; Baumgartner, J.W.; Presnell, S.R.; Schrader, S.K.; Yamagiwa, T.; Whitmore, T.E.; O'Hara, P.J.; Foster, D.F. Cloning and characterization of a novel class I cytokine receptor. Biochem. Biophys. Res. Commun., 1998, 246, 82-90.
129. Ruckerl, D.; Hessmann, M.; Yoshimoto, T.; Ehlers, S.; Holscher, C. Alternatively activated macrophages express the IL-27 receptor alpha chain WSX-1. Immunobiology, 2006, 211, 427-436.
130. Yoshida, H.; Hamano, S.; Senaldi, G.; Covey, T.; Faggioni, R.; Mu, S.; Xia, M.; Wakeham, A.C.; Nishina, H.; Potter, J.; Saris, C.J.; Mak, T.W. WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection. Immunity, 2001, 15, 569-578.
131. Larousserie, F.; Charlot, P.; Bardel, E.; Froger, J.; Kastelein, R.A.; Devergne, O. Differential effects of IL-27 on human B cell subsets. J. Immunol., 2006, 176, 5890-5897.
132. Takeda, A.; Hamano, S.; Yamanaka, A.; Hanada, T.; Ishibashi, T.; Mak, T.W.; Yoshimura, A.; Yoshida, H. Cutting edge: role of IL-27/WSX-1 signalling for induction of T-bet through activation of STAT1 during initial Th1 commitment. J. Immunol., 2003, 170, 4886-4890.
133. Takeda, A.; Hamano, S.; Shiraishi, H.; Yoshimura, T.; Ogata, H.; Ishii, K.; Ishibashi, T.; Yoshimura, A.; Yoshida, H. WSX-1 over-expression in CD4(+) T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation. Int. Immunol., 2005, 17, 889-897.
134. Hibbert, L.; Pflanz, S.; de Waal, M.R.; Kastelein, R.A. IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells. J. Interferon Cytokine Res., 2003, 23, 513-522.
135. Kamiya, S.; Owaki, T.; Morishima, N.; Fukai, F.; Mizuguchi, J.; Yoshimoto, T. An indispensable role for STAT1 in IL-27-induced T-bet expression but not proliferation of naive CD4+ T cells. J. Immunol., 2004, 173, 3871-3877.
136. Lucas, S.; Ghilardi, N.; Li, J.; De Sauvage, F.J. IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms. Proc. Natl. Acad. Sci. USA, 2003, 100, 15047-15052.
137. Holscher, C.; Holscher, A.; Ruckerl, D.; Yoshimoto, T.; Yoshida, H.; Mak, T.; Saris, C.; Ehlers, S. The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis. J. Immunol., 2005, 174, 3534-3544.
138. Yoshimura, T.; Takeda, A.; Hamano, S.; Miyazaki, Y.; Kinjyo, I.; Ishibashi, T.; Yoshimura, A.; Yoshida, H. Two-sided roles of IL-27: induction of Th1 differentiation on naive CD4+ T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4+ T cells partially through STAT3-dependent mechanism. J. Immunol., 2006, 177, 5377-5385.
139. Brender, C.; Tannahill, G.M.; Jenkins, B. J.; Fletcher, J.; Columbus, R.; Saris, C.J.; Ernst, M.; Nicola, N.A.; Hilton, D.J.; Alexander, W.S.; Starr, R. Suppressor of cytokine signalling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27. Blood, 2007, 110, 2528-2536.
140. Owaki, T.; Asakawa, M.; Kamiya, S.; Takeda, K.; Fukai, F.; Mizuguchi, J.; Yoshimoto, T. IL-27 suppresses CD28-mediated [correction of medicated] IL-2 production through suppressor of cytokine signalling 3. J. Immunol., 2006, 176, 2773-2780.
141. Villarino, A.V.; Stumhofer, J.S.; Saris, C.J.; Kastelein, R. A.; de Sauvage, F.J.; Hunter, C. A. IL-27 limits IL-2 production during Th1 differentiation. J. Immunol., 2006, 176, 237-247.
142. Siegemund, S.; Schutze, N.; Freudenberg, M.A.; Lutz, M.B.; Straubinger, R.K.; Alber, G. Production of IL-12, IL-23 and IL-27p28 by bone marrow-derived conventional dendritic cells rather than macrophages after LPS/TLR4-dependent induction by Salmonella enteritidis. Immunobiology, 2008, 212, 739-750.
143. Molle, C.; Nguyen, M.; Flamand, V.; Renneson, J.; Trottein, F.; De Wit, D.; Willems, F.; Goldman, M.; Goriely, S. IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3. J. Immunol., 2007, 178, 7607-7615.
144. Sonobe, Y.; Yawata, I.; Kawanokuchi, J.; Takeuchi, H.; Mizuno, T.; Suzumura, A. Production of IL-27 and other IL-12 family cytokines by microglia and their subpopulations. Brain Res., 2005, 1040, 202-207.
145. Liu, J.; Guan, X.; Ma, X. Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-gamma-mediated pathways. J. Exp. Med., 2007, 204, 141-152.
146. Wirtz, S.; Becker, C.; Fantini, M.C.; Nieuwenhuis, E.E.; Tubbe, I.; Galle, P.R.; Schild, H.J.; Birkenbach, M.; Blumberg, R.S.; Neurath, M.F. EBV-induced gene 3 transcription is induced by TLR signalling in primary dendritic cells via NF-kappa B activation. J. Immunol., 2005, 174, 2814-2824.
147. Owaki, T.; Asakawa, M.; Morishima, N.; Hata, K.; Fukai, F.; Matsui, M.; Mizuguchi, J.; Yoshimoto, T. A role for IL-27 in early regulation of Th1 differentiation. J. Immunol., 2005, 175, 2191-2200.
148. Batten, M.; Li, J.; Yi, S.; Kljavin, N.M.; Danilenko, D.M.; Lucas, S.; Lee, J.; de Sauvage, F.J.; Ghilardi, N. Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat. Immunol., 2006, 7, 929-936.
149. Lucas, S, Ghilardi, N.; Li, J.; De Sauvage, F.J. IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms. Proc. Natl. Acad. Sci. USA, 2003, 100, 15047-15052.
150. Yoshimoto, T.; Yoshimoto, T.; Yasuda, K.; Mizuguchi, J.; Nakanishi, K. IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: a novel therapeutic way for Th2-mediated allergic inflammation. J. Immunol., 2007, 179, 4415-4423.
151. Owaki, T.; Asakawa, M.; Fukai, F.; Mizuguchi, J.; Yoshimoto, T. IL-27 induces Th1 differentiation via p38 MAPK/T-bet- and intercellular adhesion molecule-1/LFA-1/ERK1/2-dependent pathways. J. Immunol., 2006, 177, 7579-7587.
152. Zahn, S.; Wirtz, S.; Birkenbach, M.; Blumberg, R.S.; Neurath, M.F.; von Stebut, E. Impaired Th1 responses in mice deficient in Epstein-Barr virus-induced gene 3 and challenged with physiological doses of Leishmania major. Eur. J. Immunol., 2005, 35, 1106-1112.
153. Imamichi, T.; Yang, J.; Huang, D.W.; Brann, T.W.; Fullmer, B.A.; Adelsberger, J.W.; Lempicki, R.A.; Baseler, M.W.; Lane, H.C. IL-27, a novel anti-HIV cytokine, activates multiple interferon-inducible genes in macrophages. AIDS, 2008, 22, 39-45.
154. Feng, X.M.; Liu, N.; Yang, S. G.; Hu, L.Y.; Chen, X.L.; Fang, Z.H.; Ren, Q.; Lu, S.H.; Liu, B.; Han, Z.C. Regulation of the class II and class I MHC pathways in human THP-1 monocytic cells by interleukin-27. Biochem. Biophys. Res. Commun., 2008, 367, 553-559.
155. Artis, D.; Villarino, A.; Silverman, M.; He, W.; Thornton, E.M.; Mu, S.; Summer, S.; Covey, T.M.; Huang, E.; Yoshida, H.; Koretzky, G.; Goldschmidt, M.; Wu, G.D.; De Sauvage, F.; Miller, H.R.; Saris, C.J.; Scott, P.; Hunter, C.A. The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity. J. Immunol., 2004, 173, 5626-5634.
156. Hamano, S.; Himeno, K.; Miyazaki, Y.; Ishii, K.; Yamanaka, A.; Takeda, A.; Zhang, M.; Hisaeda, H.; Mak, T.W.; Yoshimura, A.; Yoshida, H. WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production. Immunity, 2003, 19, 657-667.
157. Hamano, S.; Himeno, K.; Miyazaki, Y.; Ishii, K.; Yamanaka, A.; Takeda, A.; Zhang, M.; Hisaeda, H.; Mak, T.W.; Yoshimura, A.; Yoshida, H. WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production. Immunity, 2003, 19, 657-667.
158. Stumhofer, J.S.; Laurence, A.; Wilson, E.H.; Huang, E.; Tato, C.M.; Johnson, L.M.; Villarino, A.V.; Huang, Q.; Yoshimura, A.; Sehy, D.; Saris, C.J.; O'Shea, J.J.; Hennighausen, L.; Ernst, M.; Hunter, C.A. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat. Immunol., 2006, 7, 937-945.
159. Drogemuller, K.; Helmuth, U.; Brunn, A.; Sakowicz-Burkiewicz, M.; Gutmann, D.H.; Mueller, W.; Deckert, M.; Schluter, D. Astrocyte gp130 expression is critical for the control of Toxoplasma encephalitis. J. Immunol., 2008, 181, 2683-2693.
160. Villarino, A.; Hibbert, L.; Lieberman, L.; Wilson, E.; Mak, T.; Yoshida, H.; Kastelein, R.A.; Saris, C.; Hunter, C.A. The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Immunity, 2003, 19, 645-655.
161. Hunter, C.A.; Villarino, A.; Artis, D.; Scott, P. The role of IL-27 in the development of T-cell responses during parasitic infections. Immunol. Rev., 2004, 202,106-14.
162. Pearl, J.E.; Khader, S.A.; Solache, A.; Gilmartin, L.; Ghilardi, N.; deSauvage, F.; Cooper, A. M. IL-27 signalling compromises control of bacterial growth in mycobacteria-infected mice. J. Immunol., 2004, 173, 7490-7496.
163. Robinson, C.M.; Nau, G.J. Interleukin-12 and interleukin-27 regulate macrophage control of Mycobacterium tuberculosis. J. Infect. Dis., 2008, 198, 359-366.
164. Vignali, D.A.; Collison, L.W.; Workman, C.J. How regulatory T cells work. Nat. Rev. Immunol., 2008, 8, 523-532.
165. Bettelli, E.; Korn, T.; Oukka, M.; Kuchroo, V.K. Induction and effector functions of T(H)17 cells. Nature, 2008, 453, 1051-1057.
166. Zhang, X.; Jin, J.; Peng, X.; Ramgolam, V.S.; Markovic-Plese, S. Simvastatin inhibits IL-17 secretion by targeting multiple IL-17-regulatory cytokines and by inhibiting the expression of IL-17 transcription factor RORC in CD4+ lymphocytes. J. Immunol., 2008, 180, 6988-6996.
167. Goldberg, R.; Wildbaum, G.; Zohar, Y.; Maor, G.; Karin, N. Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of the p28 subunit of IL-27. J. Immunol., 2004, 173, 1171- 1178.
168. Cao, Y.; Doodes, P.D.; Glant, T.T.; Finnegan, A. IL-27 induces a Th1 immune response and susceptibility to experimental arthritis. J. Immunol., 2008, 180, 922-930.
169. Niedbala, W.; Cai, B.; Wei, X.; Patakas, A.; Leung, B.P.; McInnes, I.B.; Liew, F.Y. Interleukin-27 attenuates collagen-induced arthritis. Ann. Rheum. Dis., 2008, 67, 1474-1479.
170. Shimizu, S.; Sugiyama, N.; Masutani, K.; Sadanaga, A.; Miyazaki, Y.; Inoue, Y.; Akahoshi, M.; Katafuchi, R.; Hirakata, H.; Harada, M.; Hamano, S.; Nakashima, H.; Yoshida, H. Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1). J. Immunol., 2005, 175, 7185-7192.
171. Sugiyama, N.; Nakashima, H.; Yoshimura, T.; Sadanaga, A.; Shimizu, S.; Masutani, K.; Igawa, T.; Akahoshi, M.; Miyake, K.; Takeda, A.; Yoshimura, A.; Hamano, S.; Yoshida, H. Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of IL-27R{alpha} (WSX-1). Ann. Rheum. Dis., 2007, 67, 1461-1467.
172. Guo, B.; Chang, E.Y.; Cheng, G. The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. J. Clin. Invest., 2008, 118, 1680-1690.
173. Fitzgerald, D.C.; Ciric, B.; Touil, T.; Harle, H.; Grammatikopolou, J.; Das, S.J.; Gran, B.; Zhang, G.X.; Rostami, A. Suppressive effect of IL-27 on encephalitogenic Th17 cells and the effector phase of experimental autoimmune encephalomyelitis. J. Immunol., 2007, 179, 3268-3275.
174. Fitzgerald, D.C.; Zhang, G.X.; El Behi, M.; Fonseca-Kelly, Z.; Li, H.; Yu, S.; Saris, C. J.; Gran, B.; Ciric, B.; Rostami, A. Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat. Immunol., 2007, 8, 1372-1379.
175. Wang, S.; Miyazaki, Y.; Shinozaki, Y.; Yoshida, H. Augmentation of antigen-presenting and Th1-promoting functions of dendritic cells by WSX-1(IL-27R) deficiency. J. Immunol., 2007, 179, 6421-6428.
176. Yoshimoto, T.; Morishima, N.; Mizoguchi, I.; Shimizu, M.; Nagai, H.; Oniki, S.; Oka, M.; Nishigori, C.; Mizuguchi, J. Antiproliferative activity of IL-27 on melanoma. J. Immunol., 2008, 180, 6527-6535.
177. Oniki, S.; Nagai, H.; Horikawa, T.; Furukawa, J.; Belladonna, M.L.; Yoshimoto, T.; Hara, I.; Nishigori, C. Interleukin-23 and interleukin-27 exert quite different antitumour and vaccine effects on poorly immunogenic melanoma. Cancer Res., 2006, 66, 6395-6404.
178. Shimizu, M.; Shimamura, M.; Owaki, T.; Asakawa, M.; Fujita, K.; Kudo, M.; Iwakura, Y.; Takeda, Y.; Luster, A.D.; Mizuguchi, J.; Yoshimoto, T. Antiangiogenic and antitumour activities of IL-27. J. Immunol., 2006, 176, 7317-7324.
179. Weiss, J.M.; Subleski, J.J.; Wigginton, J.M.; Wiltrout, R.H. Immunotherapy of cancer by IL-12-based cytokine combinations. Expert Opin. Biol. Ther., 2007, 7, 1705-1721.
180. Morishima, N.; Owaki, T.; Asakawa, M.; Kamiya, S.; Mizuguchi, J.; Yoshimoto, T. Augmentation of effector CD8+ T cell generation with enhanced granzyme B expression by IL-27. J. Immunol., 2005, 175, 1686-1693.
181. Hisada, M.; Kamiya, S.; Fujita, K.; Belladonna, M.L.; Aoki, T.; Koyanagi, Y.; Mizuguchi, J.; Yoshimoto, T. Potent antitumour activity of interleukin-27. Cancer Res., 2004, 64, 1152-1156.
182. Salcedo, R.; Stauffer, J.K.; Lincoln, E.; Back, T.C.; Hixon, J.A.; Hahn, C.; Shafer-Weaver, K.; Malyguine, A.; Kastelein, R.; Wigginton, J.M. IL-27 mediates complete regression of orthotopic primary and metastatic murine neuroblastoma tumours: role for CD8+ T cells. J. Immunol., 2004, 173, 7170-7182.
183. Devergne, O.; Birkenbach, M.; Kieff, E. Epstein-Barr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin. Proc. Natl. Acad. Sci. USA, 1997, 94, 12041-12046.
184. Langrish, C.L.; McKenzie, B.S.; Wilson, N.J.; de Waal, M.R.; Kastelein, R.A.; Cua, D. J. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol. Rev., 2004, 202, 96-105.
185. Sigidin, Y.A.; Loukina, G.V.; Skurkovich, B.; Skurkovich, S. Randomized, double-blind trial of anti-interferon-gamma antibodies in rheumatoid arthritis. Scand. J. Rheumatol., 2001, 30, 203-207.
186. Skurkovich, S.; Boiko, A.; Beliaeva, I.; Buglak, A.; Alekseeva, T.; Smirnova, N.; Kulakova, O.; Tchechonin, V.; Gurova, O.; Deomina, T.; Favorova, O.O.; Skurkovic, B.; Gusev, E. Randomized study of antibodies to IFN-gamma and TNF-alpha in secondary progressive multiple sclerosis. Mult. Scler., 2001, 7, 277-284.
187. Murphy, C.A.; Langrish, C.L.; Chen, Y.; Blumenschein, W.; McClanahan, T.; Kastelein, R.A.; Sedgwick, J.D.; Cua, D.J. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp. Med., 2003, 198, 1951-1957.
188. Wirtz, S.; Tubbe, I.; Galle, P.R.; Schild, H. J.; Birkenbach, M.; Blumberg, R.S.; Neurath, M.F. Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27. J. Exp. Med., 2006, 203, 1875-1881.