The biology of IL-12: Coordinating innate and adaptive immune responses

Cytokine and Growth Factor Reviews

Volumn 14, Issue 5, 2003, Pages 361-368

  Watford, Wendy T ^a   Moriguchi, Masato ^a   Morinobu, Akio ^a   O'Shea, John J ^a  

^a NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES   (United States)

Author keywords

IL 12; IL 23; IL 27; Interferon ; T helper 1 cells

Indexed keywords

CD4 ANTIGEN; CYTOKINE; GAMMA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 12 RECEPTOR; INTERLEUKIN 23; INTERLEUKIN 27; UNCLASSIFIED DRUG;

CELL DIFFERENTIATION; CELL MATURATION; CELL PROLIFERATION; CELLULAR IMMUNITY; CYTOKINE PRODUCTION; DENDRITIC CELL; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; INFECTION; INTERFERON PRODUCTION; LYMPHOID CELL; MACROPHAGE; MEMORY CELL; NATURAL KILLER CELL; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN STRUCTURE; SHORT SURVEY; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; TH1 CELL;

EID: 0042375986     PISSN: 13596101     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1359-6101(03)00043-1     Document Type: Short Survey

References (111)

1. Gately MK, et al. Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor). J Immunol 1991;147(3):874-82.
2. Gubler U, et al. Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. Proc Natl Acad Sci USA 1991;88(10):4143-7.
3. Wolf SF, et al. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol 1991;146(9):3074-81.
4. Trinchieri G, Scott P. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions. Res Immunol 1995;146(7-8):423-31.
5. Trinchieri G, Scott P. Interleukin-12: basic principles and clinical applications. Curr Top Microbiol Immunol 1999;238:57-78.
6. Esche C, Shurin MR, Lotze MT. IL-12. In: Oppenheim JJ, Feldmann M, editors. Cytokine reference. San Diego: Academic Press; 2000. p. 189-201.
7. Merberg DM, Wolf SF, Clark SC. Sequence similarity between NKSF and the IL-6/G-CSF family. Immunol Today 1992;13(2): 77-8.
8. Gately MK, et al. Interleukin-12 antagonist activity of mouse interleukin-12p40 homodimer in vitro and in vivo. Ann NY Acad Sci 1996;795:1-12.
9. Ling P, et al. Human IL-12p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity. J Immunol 1995;154(1):116-27.
10. Ha SJ, et al. A novel function of IL-12p40 as a chemotactic molecule for macrophages. J Immunol 1999;163(5):2902-8.
11. Murphy TL, et al. Regulation of interleukin-12p40 expression through an NF-κB half-site. Mol Cell Biol 1995;15(10):5258-67.
12. Ma X, et al. The interleukin-12 p40 gene promoter is primed by interferon-γ in monocytic cells. J Exp Med 1996;183(1):147-57.
13. Ma X, et al. Identification and characterization of a novel Ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene promoter. J Biol Chem 1997;272(16):10389-95.
14. Plevy SE, et al. Multiple control elements mediate activation of the murine and human interleukin-12 p40 promoters: evidence of functional synergy between C/EBP and Rel proteins. Mol Cell Biol 1997;17(8):4572-88.
15. Wang IM, et al. An IFN-γ-inducible transcription factor, IFN consensus sequence binding protein (ICSBP), stimulates IL-12p40 expression in macrophages. J Immunol 2000;165(1):271-9.
16. Gri G, et al. Synergistic regulation of the human interleukin-12 p40 promoter by NF-κB and Ets transcription factors in Epstein-Barr virus-transformed B cells and macrophages. J Biol Chem 1998;273(11):6431-8.
17. Salkowski CA, et al. IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice. J Immunol 1999;163(3):1529-36.
18. Giese NA, et al. Interferon (IFN) consensus sequence-binding protein, a transcription factor of the IFN regulatory factor family, regulates immune responses in vivo through control of interleukin-12 expression. J Exp Med 1997;186(9):1535-46.
19. Scharton-Kersten T, et al. Interferon consensus sequence binding protein-deficient mice display impaired resistance to intracellular infection due to a primary defect in interleukin-12p40 induction. J Exp Med 1997;186(9):1523-34.
20. Sanjabi S, et al. Selective requirement for c-Rel during IL-12 p40 gene induction in macrophages. Proc Natl Acad Sci USA 2000;97(23):12705-10.
21. Babik JM, et al. Expression of murine IL-12 is regulated by translational control of the p35 subunit. J Immunol 1999;162(7): 4069-78.
22. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol 2001;1(2):135-45.
23. Barton GM, Medzhitov R. Control of adaptive immune responses by Toll-like receptors. Curr Opin Immunol 2002;14(3):380-3.
24. Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001;2(8): 675-80.
25. Scanga CA, et al. Cutting edge: MyD88 is required for resistance to Toxoplasma gondii infection and regulates parasite-induced IL-12 production by dendritic cells. J Immunol 2002;168(12):5997-6001.
26. Jacobson NG, et al. Interleukin-12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (STAT)3 and STAT4. J Exp Med 1995;181(5):1755-62.
27. Cella M, et al. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med 1996;184(2):747-52.
28. Yoshida A, et al. IFN-γ induces IL-12 mRNA expression by a murine macrophage cell line, J774. Biochem Biophys Res Commun 1994;198(3):857-61.
29. Kubin M, Chow JM, Trinchieri G. Differential regulation of interleukin-12 (IL-12), tumor necrosis factor-α, and IL-1β production in human myeloid leukemia cell lines and peripheral blood mononuclear cells. Blood 1994;83(7):1847-55.
30. D'Andrea A, et al. Stimulatory and inhibitory effects of interleukin-4 (IL-4) and IL-13 on the production of cytokines by human peripheral blood mononuclear cells: priming for IL-12 and tumor necrosis factor alpha production. J Exp Med 1995;181(2):537-46.
31. Takenaka H, et al. Regulation of T cell-dependent and -independent IL-12 production by the three Th2-type cytokines IL-10, IL-6, and IL-4. J Leuk Biol 1997;61(1):80-7.
32. Hochrein H, et al. Interleukin-4 (IL-4) is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells. J Exp Med 2000;192(6):823-33.
33. Marshall JD, et al. Priming with IL-4 and IL-13 during HIV-1 infection restores in vitro IL-12 production by mononuclear cells of HIV-infected patients. J Immunol 1997;159(11):5705-14.
34. Major J, Fletcher JE, Hamilton TA. IL-4 pretreatment selectively enhances cytokine and chemokine production in lipopolysaccharide-stimulated mouse peritoneal macrophages. J Immunol 2002;168(5): 2456-63.
35. Koch F, et al. High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J Exp Med 1996;184(2):741-6.
36. Snijders A, et al. Regulation of bioactive IL-12 production in lipopolysaccharide-stimulated human monocytes is determined by the expression of the p35 subunit. J Immunol 1996;156(3):1207-12.
37. Schindler H, et al. The production of IFN-γ by IL-12-IL-18-activated macrophages requires STAT4 signaling and is inhibited by IL-4. J Immunol 2001;166(5):3075-82.
38. Aliberti J, Sher A. Positive and negative regulation of pathogen induced dendritic cell function by G-protein coupled receptors. Mol Immunol 2002;38(12-13):891-3.
39. Micallef MJ, et al. Interferon-γ-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-γ production. Eur J Immunol 1996;26(7):1647-51.
40. Robinson D, et al. IGIF does not drive Th1 development but synergizes with IL-12 for interferon-γ production and activates IRAK and NF-κB. Immunity 1997;7(4):571-81.
41. Lauwerys BR, Renauld JC, Houssiau FA. Synergistic proliferation and activation of natural killer cells by interleukin-12 and interleukin-18. Cytokine 1999;11(11):822-30.
42. Yoshimoto T, et al. Interleukin-18 together with interleukin-12 inhibits IgE production by induction of interferon-γ production from activated B cells. Proc Natl Acad Sci USA 1997;94(8):3948-53.
43. Lawless VA, et al. STAT4 regulates multiple components of IFN-γ-inducing signaling pathways. J Immunol 2000;165(12): 6803-8.
44. Fukao T, et al. Inducible expression of STAT4 in dendritic cells and macrophages and its critical role in innate and adaptive immune responses. J Immunol 2001;166(7):4446-55.
45. Frucht DM, et al. IFN-γ production by antigen-presenting cells: mechanisms emerge. Trends Immunol 2001;22(10):556-60.
46. Grohmann U, et al. IL-12 acts directly on DC to promote nuclear localization of NF-κB and primes DC for IL-12 production. Immunity 1998;9(3):315-23.
47. Dong C, Flavell RA. Th1 and Th2 cells. Curr Opin Hematol 2001;8(1):47-51.
48. Glimcher LH. Lineage commitment in lymphocytes: controlling the immune response. J Clin Invest 2001;108(7):s25-30.
49. O'Shea JJ, Gadina M, Schreiber RD. Cytokine signaling in 2002: new surprises in the JAK-STAT pathway. Cell 2002;109(Suppl): S121-131.
50. O'Shea JJ, Paul WE. Regulation of T(H)1 differentiation controlling the controllers. Nat Immunol 2002;3(6):506-8.
51. Farrar JD, Asnagli H, Murphy KM. T helper subset development: roles of instruction, selection, and transcription. J Clin Invest 2002;109(4):431-5.
52. Ho IC, Glimcher LH. Transcription: tantalizing times for T cells. Cell 2002;109(Suppl):S109-120.
53. Chua AO, et al. Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130. J Immunol 1994;153(1):128-36.
54. Chua AO, et al. Cloning and characterization of a mouse IL-12 receptor-β component. J Immunol 1995;155(9):4286-94.
55. Presky DH, et al. A functional interleukin-12 receptor complex is composed of two β-type cytokine receptor subunits. Proc Natl Acad Sci USA 1996;93(24):14002-7.
56. Esche C, Shurin MR, Lotze MT. IL-12 Receptor. In: Oppenheim JJ, Feldmann M, editors. Cytokine reference. San Diego: Academic Press; 2000.
57. Naeger LK, et al. Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling. J Biol Chem 1999;274(4):1875-8.
58. Nishikomori R, et al. Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12Rβ2 chain expression and signaling. J Immunol 2002;169(8):4388-98.
59. Wu C, et al. IL-12 receptor beta 2 (IL-12Rβ2)-deficient mice are defective in IL-12-mediated signaling despite the presence of high affinity IL-12 binding sites. J Immunol 2000;165(11):6221-8.
60. Rogge L, et al. Antibodies to the IL-12 receptor β2 chain mark human Th1 but not Th2 cells in vitro and in vivo. J Immunol 1999;162(7):3926-32.
61. Lighvani AA, et al. T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells. Proc Natl Acad Sci USA 2001;98(26):15137-42.
62. + T cells. Nat Immunol; 2002.
63. Szabo SJ, et al, Regulation of the interleukin (IL)-12Rβ2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 1997;185(5):817-24.
64. Rogge L, et al. Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J Exp Med 1997;185(5): 825-31.
65. Sinigaglia F, et al. Regulation of the IL-12-IL-12R axis: a critical step in T-helper cell differentiation and effector function. Immunol Rev 1999;170:65-72.
66. Nishikomori R, et al. BALB/c mice bearing a transgenic IL-12 receptor β2 gene exhibit a non-healing phenotype to Leishmania major infection despite intact IL-12 signaling. J Immunol 2001;166(11):6776-83.
67. Nishikomori R, Ehrhardt RO, Strober W. T helper type 2 cell differentiation occurs in the presence of interleukin-12 receptor β2 chain expression and signaling. J Exp Med 2000;191(5):847-58.
68. Bacon CM, et al. 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(1): 399-404.
69. Zou J, et al. Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits β1 and β2 and JAK kinases. J Biol Chem 1997;272(9):6073-7.
70. Leonard WJ, O'Shea JJ. JAKs and STATs: biological implications. Annu Rev Immunol 1998;16:293-322.
71. Bacon CM, et al. Interleukin-12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes. Proc Natl Acad Sci USA 1995;92(16):7307-11.
72. Thierfelder WE, et al. Requirement for STAT4 in interleukin-12-mediated responses of natural killer and T cells. Nature 1996;382(6587):171-4.
73. Kaplan MH, et al. Impaired IL-12 responses and enhanced development of Th2 cells in STAT4-deficient mice. Nature 1996;382(6587):174-7.
74. Nguyen KB, et al. Critical role for STAT4 activation by type 1 interferons in the interferon-γ response to viral infection. Science 2002;297(5589):2063-6.
75. Xu X, Sun YL, Hoey T. Cooperative DNA binding and sequence-selective recognition conferred by the STAT amino-terminal domain. Science 1996;273(5276):794-7.
76. Pignata C, et al. Phosphorylation of src family lck tyrosine kinase following interleukin-12 activation of human natural killer cells. Cell Immunol 1995;165(2):211-6.
77. Gollob JA, et al. The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated protein kinase and is associated with the augmentation of STAT serine phosphorylation. J Immunol 1999;162(8):4472-81.
78. Zhang S, Kaplan MH. The p38 mitogen-activated protein kinase is required for IL-12-induced IFN-γ expression. J Immunol 2000;165(3):1374-80.
79. Visconti R, et al. Importance of the MKK6-p38 pathway for interleukin-12-induced STAT4 serine phosphorylation and transcriptional activity. Blood 2000;96(5):1844-52.
80. Morinobu A, et al. STAT4 serine phosphorylation is critical for IL-12-induced IFN-γ production but not for cell proliferation. Proc Natl Acad Sci USA 2002;99(19):12281-6.
81. Oppmann B, et al. 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(5):715-25.
82. Belladonna ML, et al. IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells. J Immunol 2002;168(11):5448-54.
83. Parham C, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R. J Immunol 2002;168(11):5699-708.
84. + T cells. Immunity 2002;16:779-90.
85. 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(22):12041-6.
86. Devergne O, et al. A novel interleukin-12p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes. J Virol 1996;70(2):1143-53.
87. Yoshida H, et al. WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection. Immunity 2001;15(4):569-78.
88. Chen Q, et al. Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 2000;407(6806):916-20.
89. Mattner F, et al. 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(7):1553-9.
90. Magram J, et al. IL-12-deficient mice are defective in IFN-γ production and type 1 cytokine responses. Immunity 1996;4(5): 471-81.
91. Wu C, et al. Characterization of IL-12 receptorβ1 chain (IL-12Rβ1)-deficient mice: IL-12Rβ1 is an essential component of the functional mouse IL-12 receptor. J Immunol 1997;159(4): 1658-65.
92. Wu CY, et al. Cytokine regulation of IL-12Rβ2 expression: differential effects on human T and NK cells. Eur J Immunol 2000;30(5):1364-74.
93. Decken K, et al. Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans. Infect Immunol 1998;66(10):4994-5000.
94. Piccotti JR, et al. Alloantigen-reactive Th1 development in IL-12-deficient mice. J Immunol 1998;160(3):1132-8.
95. Camoglio L, et al. Contrasting roles of IL-12p40 and IL-12p35 in the development of hapten-induced colitis. Eur J Immunol 2002;32(1):261-9.
96. Frucht DM. IL-23: a cytokine that acts on memory T cells. Sci STKE 2002;2002(114):PE1.
97. de Jong R, et al. Severe mycobacterial and Salmonella infections in interleukin-12R-deficient patients. Science 1998;280(5368):1435-8.
98. Doffinger R, et al. Inherited disorders of IL-12-and IFN-γ -mediated immunity: a molecular genetics update. Mol Immunol 2002;38(12-13): 903-9.
99. Becher B, Durell BG, Noelle RJ. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J Clin Invest 2002;110(4):493-7.
100. Matsui E, et al. Reduced IFN-γ production in response to IL-12 stimulation and/or reduced IL-12 production in atopic patients. Clin Exp Allergy 2000;30(9):1250-6.
101. Kondo N, et al. Atopy and mutations of IL-12Rβ2 chain gene. Clin Exp Allergy 2001;31(8):1189-93.
102. Neubauer H, et al. JAK2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 1998;93(3):397-409.
103. Parganas E, et al. JAK2 is essential for signaling through a variety of cytokine receptors. Cell 1998;93(3):385-95.
104. Shimoda K, et al. TYK2 plays a restricted role in IFN-α signaling, although it is required for IL-12-mediated T cell function. Immunity 2000;13(4):561-71.
105. Karaghiosoff M, et al. Partial impairment of cytokine responses in TYK2-deficient mice. Immunity 2000;13(4):549-60.
106. Shimoda K, et al. Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in TYK2-deficient mice. Blood 2002;99(6): 2094-9.
107. Nakahira M, et al. An absolute requirement for STAT4 and a role for IFN-γ as an amplifying factor in IL-12 induction of the functional IL-18 receptor complex. J Immunol 2001;167(3):1306-12.
108. Iwasaki M, et al. A mandatory role for STAT4 in IL-12 induction of mouse T cell CCR5. J Immunol 2001;167(12):6877-83.
109. Lim YC, et al. IL-12, STAT4-dependent up-regulation of CD4(+) T cell core 2β-1,6-n-acetylglucosaminyltransferase, an enzyme essential for biosynthesis of P-selectin ligands. J Immunol 2001;167(8):4476-84.
110. White SJ, et al. Cutting edge: differential requirements for STAT4 in expression of glycosyltransferases responsible for selectin ligand formation in Th1 cells. J Immunol 2001;167(2):628-31.
111. Nakahira M, et al. Synergy of IL-12 and IL-18 for IFN-γ gene expression: IL-12-induced STAT4 contributes to IFN-γ promoter activation by up-regulating the binding activity of IL-18-induced activator protein 1. J Immunol 2002;168(3):1146-53.