, Volume 31, Issue 4, pp 235–246 | Cite as

LPS and Poly I:C Induce Chromatin Modifications at a Novel Upstream Region of the IL-23 p19 Promoter

  • Stacey Garrett
  • Michael C. Fitzgerald
  • Kathleen E. Sullivan


IL-23, a heterodimer of IL-12 p40 and IL-23 p19, is critical for an effective immune response to many infections and has been implicated in several autoimmune diseases, however, little is known about the regulation of IL-23 gene expression in monocytes. We found that poly I:C, LPS, flagellin, and zymogen activated significant IL-23 production in primary human monocytes. Using chromatin immunoprecipitation, we found that a distal upstream region of the IL-23 p19 promoter at −601 to −521 underwent extensive histone modifications in response to stimuli. This distal region of the promoter is not highly conserved between species and has not been previously implicated in the regulation of IL-23 expression. Knockdown of CBP markedly decreased IL-23 p19 responses to poly I:C but had a less dramatic effect on LPS responses, confirming different chromatin responses to these two stimuli. Our data suggest that one of the mechanisms regulating IL-23 expression is the regulation of histone modifications at this distal upstream region of the promoter.


human monocyte/macrophages cytokines histones chromatin gene regulation molecular biology CBP 



This work was supported by NIH grants AI051323 and AI44127. The authors wish to acknowledge the Human Immunology Core at the University of Pennsylvania, which provided the primary monocytes for this study. Stacey Garrett was supported in part by The University of Pennsylvania School of Medicine Cancer Research Institute Predoctoral Emphasis on Pathways in Tumor Immunology Training Grant.

Authors’ Contributions

SG carried out the ChIP studies and drafted the manuscript. MF performed the knockdown and the RT-PCR experiments. KS provided oversight of the study design and final wording of the text. All authors read and approved the final manuscript.


  1. 1.
    Birney, E. 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816.PubMedCrossRefGoogle Scholar
  2. 2.
    Albrecht, I., T. Tapmeier, S. Zimmermann, M. Frey, K. Heeg, and A. Dalpke. 2004. Toll-like receptors differentially induce nucleosome remodelling at the IL-12p40 promoter. EMBO Reports 5:172–177.PubMedCrossRefGoogle Scholar
  3. 3.
    Altare, F., D. Lammas, P. Revy, E. Jouanguy, R. Doffinger, S. Lamhamedi, P. Drysdale, D. Scheel-Toellner, J. Girdlestone, P. Darbyshire, M. Wadhwa, H. Dockrell, M. Salmon, A. Fischer, A. Durandy, J. L. Casanova, and D. S. Kumararatne. 1998. Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J. Clin. Invest. 102:2035–2040.PubMedCrossRefGoogle Scholar
  4. 4.
    Andersson, A., R. Kokkola, J. Wefer, H. Erlandsson-Harris, and R. A. Harris. 2004. Differential macrophage expression of IL-12 and IL-23 upon innate immune activation defines rat autoimmune susceptibility. J. Leukoc. Biol. 76:1118–1124.PubMedCrossRefGoogle Scholar
  5. 5.
    Belladonna, M. L., J. C. Renauld, R. Bianchi, C. Vacca, F. Fallarino, C. Orabona, M. C. Fioretti, U. Grohmann, and P. Puccetti. 2002. IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells. J. Immunol. 168:5448–5454.PubMedGoogle Scholar
  6. 6.
    Bernstein, B. E., E. L. Humphrey, R. L. Erlich, R. Schneider, P. Bouman, J. S. Liu, T. Kouzarides, and S. L. Schreiber. 2002. Methylation of histone H3 Lys 4 in coding regions of active genes. Proc. Natl. Acad. Sci. U. S. A. 99:8695–8700.PubMedCrossRefGoogle Scholar
  7. 7.
    Bernstein, B. E., M. Kamal, K. Lindblad-Toh, S. Bekiranov, D. K. Bailey, D. J. Huebert, S. McMahon, E. K. Karlsson, E. J. Kulbokas, 3rd, T. R. Gingeras, S. L. Schreiber, and E. S. Lander. 2005. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120:169–181.PubMedCrossRefGoogle Scholar
  8. 8.
    Billich, A. 2007. Drug evaluation: Apilimod, an oral IL-12/IL-23 inhibitor for the treatment of autoimmune diseases and common variable immunodeficiency. IDrugs 10:53–59.PubMedGoogle Scholar
  9. 9.
    Butchar, J. P., M. V. Rajaram, L. P. Ganesan, K. V. Parsa, C. D. Clay, L. S. Schlesinger, and S. Tridandapani. 2007. Francisella tularensis induces IL-23 production in human monocytes. J. Immunol. 178:4445–4454.PubMedGoogle Scholar
  10. 10.
    Carmody, R. J., Q. Ruan, H. C. Liou, and Y. H. Chen. 2007. Essential roles of c-Rel in TLR-induced IL-23 p19 gene expression in dendritic cells. J. Immunol. 178:186–191.PubMedGoogle Scholar
  11. 11.
    Couronne, O., A. Poliakov, N. Bray, T. Ishkhanov, D. Ryaboy, E. Rubin, L. Pachter, and I. Dubchak. 2003. Strategies and tools for whole-genome alignments. Genome. Res. 13:73–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Cua, D. J., J. Sherlock, Y. Chen, C. A. Murphy, B. Joyce, B. Seymour, L. Lucian, W. To, S. Kwan, T. Churakova, S. Zurawski, M. Wiekowski, S. A. Lira, D. Gorman, R. A. Kastelein, and J. D. Sedgwick. 2003. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748.PubMedCrossRefGoogle Scholar
  13. 13.
    de Jong, R., F. Altare, I. A. Haagen, D. G. Elferink, T. Boer, P. J. van Breda Vriesman, P. J. Kabel, J. M. Draaisma, J. T. van Dissel, F. P. Kroon, J. L. Casanova, and T. H. Ottenhoff. 1998. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 280:1435–1438.PubMedCrossRefGoogle Scholar
  14. 14.
    Decken, K., G. Kohler, K. Palmer-Lehmann, A. Wunderlin, F. Mattner, J. Magram, M. K. Gately, and G. Alber. 1998. Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans. Infect. Immun. 66:4994–5000.PubMedGoogle Scholar
  15. 15.
    Deering, R. P., and J. S. Orange. 2006. Development of a clinical assay to evaluate toll-like receptor function. Clin. Vaccine Immunol. 13:68–76.PubMedCrossRefGoogle Scholar
  16. 16.
    Duerr, R. H., K. D. Taylor, S. R. Brant, J. D. Rioux, M. S. Silverberg, M. J. Daly, A. H. Steinhart, C. Abraham, M. Regueiro, A. Griffiths, T. Dassopoulos, A. Bitton, H. Yang, S. Targan, L. W. Datta, E. O. Kistner, L. P. Schumm, A. T. Lee, P. K. Gregersen, M. M. Barmada, J. I. Rotter, D. L. Nicolae, and J. H. Cho. 2006. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463.PubMedCrossRefGoogle Scholar
  17. 17.
    Elkins, K. L., A. Cooper, S. M. Colombini, S. C. Cowley, and T. L. Kieffer. 2002. In vivo clearance of an intracellular bacterium, Francisella tularensis LVS, is dependent on the p40 subunit of interleukin-12 (IL-12) but not on IL-12 p70. Infect. Immun. 70:1936–1948.PubMedCrossRefGoogle Scholar
  18. 18.
    Gafa, V., R. Lande, M. C. Gagliardi, M. Severa, E. Giacomini, M. E. Remoli, R. Nisini, C. Ramoni, P. Di Francesco, D. Aldebert, R. Grillot, and E. M. Coccia. 2006. Human dendritic cells following Aspergillus fumigatus infection express the CCR7 receptor and a differential pattern of interleukin-12 (IL-12), IL-23, and IL-27 cytokines, which lead to a Th1 response. Infect. Immun. 74:1480–1489.PubMedCrossRefGoogle Scholar
  19. 19.
    Goodridge, H. S., W. Harnett, F. Y. Liew, and M. M. Harnett. 2003. Differential regulation of interleukin-12 p40 and p35 induction via Erk mitogen-activated protein kinase-dependent and -independent mechanisms and the implications for bioactive IL-12 and IL-23 responses. Immunology 109:415–425.PubMedCrossRefGoogle Scholar
  20. 20.
    Goriely, S., D. Demonte, S. Nizet, D. De Wit, F. Willems, M. Goldman, and C. Van Lint. 2003. Human IL-12(p35) gene activation involves selective remodeling of a single nucleosome within a region of the promoter containing critical Sp1-binding sites. Blood 101:4894–4902.PubMedCrossRefGoogle Scholar
  21. 21.
    Grumont, R., H. Hochrein, M. O’Keeffe, R. Gugasyan, C. White, I. Caminschi, W. Cook, and S. Gerondakis. 2001. c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription. J. Exp. Med. 194:1021–1032.PubMedCrossRefGoogle Scholar
  22. 22.
    Heintzman, N. D., R. K. Stuart, G. Hon, Y. Fu, C. W. Ching, R. D. Hawkins, L. O. Barrera, S. Van Calcar, C. Qu, K. A. Ching, W. Wang, Z. Weng, R. D. Green, G. E. Crawford, and B. Ren. 2007. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 39:311–318.PubMedCrossRefGoogle Scholar
  23. 23.
    Holscher, C., R. A. Atkinson, B. Arendse, N. Brown, E. Myburgh, G. Alber, and F. Brombacher. 2001. A protective and agonistic function of IL-12p40 in mycobacterial infection. J. Immunol. 167:6957–6966.PubMedGoogle Scholar
  24. 24.
    Kadowaki, N., S. Ho, S. Antonenko, R. W. Malefyt, R. A. Kastelein, F. Bazan, and Y. J. Liu. 2001. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J. Exp. Med. 194:863–869.PubMedCrossRefGoogle Scholar
  25. 25.
    Kastelein, R. A., C. A. Hunter, and D. J. Cua. 2007. Discovery and biology of IL-23 and IL-27: Related but functionally distinct regulators of inflammation. Annu. Rev. Immunol. 25:221–242.PubMedCrossRefGoogle Scholar
  26. 26.
    Khader, S. A., G. K. Bell, J. E. Pearl, J. J. Fountain, J. Rangel-Moreno, G. E. Cilley, F. Shen, S. M. Eaton, S. L. Gaffen, S. L. Swain, R. M. Locksley, L. Haynes, T. D. Randall, and A. M. Cooper. 2007. IL-23 and IL-17 in the establishment of protective pulmonary CD4+T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat. Immunol. 8:369–377.PubMedCrossRefGoogle Scholar
  27. 27.
    Kleinschek, M. A., U. Muller, S. J. Brodie, W. Stenzel, G. Kohler, W. M. Blumenschein, R. K. Straubinger, T. McClanahan, R. A. Kastelein, and G. Alber. 2006. IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12. J. Immunol. 176:1098–1106.PubMedGoogle Scholar
  28. 28.
    Kopp, T., P. Lenz, C. Bello-Fernandez, R. A. Kastelein, T. S. Kupper, and G. Stingl. 2003. IL-23 production by cosecretion of endogenous p19 and transgenic p40 in keratin 14/p40 transgenic mice: Evidence for enhanced cutaneous immunity. J. Immunol. 170:5438–5444.PubMedGoogle Scholar
  29. 29.
    Kouzarides, T. 2007. Chromatin modifications and their function. Cell 128:693–705.PubMedCrossRefGoogle Scholar
  30. 30.
    Langrish, C. L., Y. Chen, W. M. Blumenschein, J. Mattson, B. Basham, J. D. Sedgwick, T. McClanahan, R. A. Kastelein, and D. J. Cua. 2005. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201:233–240.PubMedCrossRefGoogle Scholar
  31. 31.
    Lapenta, C., S. M. Santini, M. Spada, S. Donati, F. Urbani, D. Accapezzato, D. Franceschini, M. Andreotti, V. Barnaba, and F. Belardelli. 2006. IFN-alpha-conditioned dendritic cells are highly efficient in inducing cross-priming CD8(+) T cells against exogenous viral antigens. Eur. J. Immunol. 36:2046–2060.PubMedCrossRefGoogle Scholar
  32. 32.
    Lehmann, J., S. Bellmann, C. Werner, R. Schroder, N. Schutze, and G. Alber. 2001. IL-12p40-dependent agonistic effects on the development of protective innate and adaptive immunity against Salmonella enteritidis. J. Immunol. 167:5304–5315.PubMedGoogle Scholar
  33. 33.
    Lehner, M., P. Morhart, A. Stilper, D. Petermann, P. Weller, D. Stachel, and W. Holter. 2007. Efficient chemokine-dependent migration and primary and secondary IL-12 secretion by human dendritic cells stimulated through Toll-like receptors. J. Immunother. (1997) 30:312–322.CrossRefGoogle Scholar
  34. 34.
    Leibundgut-Landmann, S., O. Gross, M. J. Robinson, F. Osorio, E. C. Slack, S. V. Tsoni, E. Schweighoffer, V. Tybulewicz, G. D. Brown, J. Ruland, and E. S. C. Reis. 2007. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat. Immunol. 8:630–638.PubMedCrossRefGoogle Scholar
  35. 35.
    Li, B., M. Carey, and J. L. Workman. 2007. The role of chromatin during transcription. Cell 128:707–719.PubMedCrossRefGoogle Scholar
  36. 36.
    Lieberman, L. A., F. Cardillo, A. M. Owyang, D. M. Rennick, D. J. Cua, R. A. Kastelein, and C. A. Hunter. 2004. IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12. J. Immunol. 173:1887–1893.PubMedGoogle Scholar
  37. 37.
    Liu, F. L., C. H. Chen, S. J. Chu, J. H. Chen, J. H. Lai, H. K. Sytwu, and D. M. Chang. 2007. Interleukin (IL)-23 p19 expression induced by IL-1{beta} in human fibroblast-like synoviocytes with rheumatoid arthritis via active nuclear factor-{kappa}B and AP-1 dependent pathway. Rheumatology 46(8):1266–1273.PubMedCrossRefGoogle Scholar
  38. 38.
    Martin, M., K. Rehani, R. S. Jope, and S. M. Michalek. 2005. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat. Immunol. 6:777–784.PubMedCrossRefGoogle Scholar
  39. 39.
    McGovern, D., and F. Powrie. 2007. The IL23 axis plays a key role in the pathogenesis of IBD. Gut 56:1333–1336.PubMedCrossRefGoogle Scholar
  40. 40.
    McKenzie, B. S., R. A. Kastelein, and D. J. Cua. 2006. Understanding the IL-23-IL-17 immune pathway. Trends. Immunol. 27:17–23.PubMedCrossRefGoogle Scholar
  41. 41.
    Mise-Omata, S., E. Kuroda, J. Niikura, U. Yamashita, Y. Obata, and T. S. Doi. 2007. A proximal kappaB site in the IL-23 p19 promoter is responsible for RelA- and c-Rel-dependent transcription. J. Immunol. 179:6596–6603.PubMedGoogle Scholar
  42. 42.
    Morris, K. V., S. W. Chan, S. E. Jacobsen, and D. J. Looney. 2004. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305:1289–1292.PubMedCrossRefGoogle Scholar
  43. 43.
    Murphy, C. A., C. L. Langrish, Y. Chen, W. Blumenschein, T. McClanahan, R. A. Kastelein, J. D. Sedgwick, and D. J. Cua. 2003. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp. Med. 198:1951–1957.PubMedCrossRefGoogle Scholar
  44. 44.
    Nakano, N., C. Nishiyama, S. Kanada, Y. Niwa, N. Shimokawa, H. Ushio, M. Nishiyama, K. Okumura, and H. Ogawa. 2007. Involvement of mast cells in IL-12/23 p40 production is essential for survival from polymicrobial infections. Blood 109:4846–4855.PubMedCrossRefGoogle Scholar
  45. 45.
    O’Neill, L. P., and B. M. Turner. 1995. Histone H4 acetylation distinguishes coding regions of the human genome from heterochromatin in a differentiation-dependent but transcription-independent manner. EMBO. J. 14:3946–3957.PubMedGoogle Scholar
  46. 46.
    Picard, C., C. Fieschi, F. Altare, S. Al-Jumaah, S. Al-Hajjar, J. Feinberg, S. Dupuis, C. Soudais, I. Z. Al-Mohsen, E. Genin, D. Lammas, D. S. Kumararatne, T. Leclerc, A. Rafii, H. Frayha, B. Murugasu, L. B. Wah, R. Sinniah, M. Loubser, E. Okamoto, A. Al-Ghonaium, H. Tufenkeji, L. Abel, and J. L. Casanova. 2002. Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. Am. J. Hum. Genet. 70:336–348.PubMedCrossRefGoogle Scholar
  47. 47.
    Pirhonen, J., S. Matikainen, and I. Julkunen. 2002. Regulation of virus-induced IL-12 and IL-23 expression in human macrophages. J. Immunol. 169:5673–5678.PubMedGoogle Scholar
  48. 48.
    Rudner, X. L., K. I. Happel, E. A. Young, and J. E. Shellito. 2007. Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect. Immun. 75:3055–3061.PubMedCrossRefGoogle Scholar
  49. 49.
    Schneider, R., A. J. Bannister, F. A. Myers, A. W. Thorne, C. Crane-Robinson, and T. Kouzarides. 2004. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat. Cell Biol. 6:73–77.PubMedCrossRefGoogle Scholar
  50. 50.
    Schuetze, N., S. Schoeneberger, U. Mueller, M. A. Freudenberg, G. Alber, and R. K. Straubinger. 2005. IL-12 family members: Differential kinetics of their TLR4-mediated induction by Salmonella enteritidis and the impact of IL-10 in bone marrow-derived macrophages. Intern. Immunol. 17:649–659.CrossRefGoogle Scholar
  51. 51.
    Smits, H. H., A. J. van Beelen, C. Hessle, R. Westland, E. de Jong, E. Soeteman, A. Wold, E. A. Wierenga, and M. L. Kapsenberg. 2004. Commensal Gram-negative bacteria prime human dendritic cells for enhanced IL-23 and IL-27 expression and enhanced Th1 development. Eur. J. Immunol. 34:1371–1380.PubMedCrossRefGoogle Scholar
  52. 52.
    Suhara, W., M. Yoneyama, I. Kitabayashi, and T. Fujita. 2002. Direct involvement of CREB-binding protein/p300 in sequence-specific DNA binding of virus-activated interferon regulatory factor-3 holocomplex. J. Biol. Chem. 277:22304–22313.PubMedCrossRefGoogle Scholar
  53. 53.
    Sullivan, K. E., A. B. Reddy, K. Dietzmann, A. R. Suriano, V. P. Kocieda, M. Stewart, and M. Bhatia. 2007. Epigenetic regulation of tumor necrosis factor alpha. Mol. Cell. Biol. 27:5147–5160.PubMedCrossRefGoogle Scholar
  54. 54.
    Sutton, C., C. Brereton, B. Keogh, K. H. Mills, and E. C. Lavelle. 2006. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 203:1685–1691.PubMedCrossRefGoogle Scholar
  55. 55.
    Takeda, K., and S. Akira. 2004. TLR signaling pathways. Semin. Immunol. 16:3–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Uhlig, H. H., B. S. McKenzie, S. Hue, C. Thompson, B. Joyce-Shaikh, R. Stepankova, N. Robinson, S. Buonocore, H. Tlaskalova-Hogenova, D. J. Cua, and F. Powrie. 2006. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25:309–318.PubMedCrossRefGoogle Scholar
  57. 57.
    Utsugi, M., K. Dobashi, T. Ishizuka, T. Kawata, T. Hisada, Y. Shimizu, A. Ono, and M. Mori. 2006. Rac1 negatively regulates lipopolysaccharide-induced IL-23 p19 expression in human macrophages and dendritic cells and NF-kappaB p65 trans activation plays a novel role. J. Immunol. 177:4550–4557.PubMedGoogle Scholar
  58. 58.
    Vanden Eijnden, S., S. Goriely, D. De Wit, M. Goldman, and F. Willems. 2006. Preferential production of the IL-12(p40)/IL-23(p19) heterodimer by dendritic cells from human newborns. Eur. J. Immunol. 36:21–26.PubMedCrossRefGoogle Scholar
  59. 59.
    Veldhoen, M., R. J. Hocking, C. J. Atkins, R. M. Locksley, and B. Stockinger. 2006. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24:179–189.PubMedCrossRefGoogle Scholar
  60. 60.
    Wada, Y., R. Lu, D. Zhou, J. Chu, T. Przewloka, S. Zhang, L. Li, Y. Wu, J. Qin, V. Balasubramanyam, J. Barsoum, and M. Ono. 2007. Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor. Blood 109:1156–1164.PubMedCrossRefGoogle Scholar
  61. 61.
    Wahl, S. M., I. M. Katona, B. M. Stadler, R. L. Wilder, W. E. Helsel, and L. M. Wahl. 1984. Isolation of human mononuclear cell subsets by counterflow centrifugal elutriation (CCE). II. Functional properties of B-lymphocyte-, T-lymphocyte-, and monocyte-enriched fractions. Cell. Imunol. 85:384–395.CrossRefGoogle Scholar
  62. 62.
    Waibler, Z., U. Kalinke, J. Will, M. H. Juan, J. M. Pfeilschifter, and H. H. Radeke. 2007. TLR-ligand stimulated interleukin-23 subunit expression and assembly is regulated differentially in murine plasmacytoid and myeloid dendritic cells. Mol. Immunol. 44:1483–1489.PubMedCrossRefGoogle Scholar
  63. 63.
    Weinmann, A. S., S. E. Plevy, and S. T. Smale. 1999. Rapid and selective remodeling of a positioned nucleosome during the induction of IL-12 p40 transcription. Immunity 11:665–675.PubMedCrossRefGoogle Scholar
  64. 64.
    Yang, C. S., C. H. Song, J. S. Lee, S. B. Jung, J. H. Oh, J. Park, H. J. Kim, J. K. Park, T. H. Paik, and E. K. Jo. 2006. Intracellular network of phosphatidylinositol 3-kinase, mammalian target of the rapamycin/70 kDa ribosomal S6 kinase 1, and mitogen-activated protein kinases pathways for regulating mycobacteria-induced IL-23 expression in human macrophages. Cell. Microbiol. 8:1158–1171.PubMedCrossRefGoogle Scholar
  65. 65.
    Zelante, T., A. De Luca, P. Bonifazi, C. Montagnoli, S. Bozza, S. Moretti, M. L. Belladonna, C. Vacca, C. Conte, P. Mosci, F. Bistoni, P. Puccetti, R. A. Kastelein, M. Kopf, and L. Romani. 2007. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur. J. Immunol. 37:2695–2706.PubMedCrossRefGoogle Scholar
  66. 66.
    Zhou, L., A. A. Nazarian, J. Xu, D. Tantin, L. M. Corcoran, and S. T. Smale. 2007. An inducible enhancer required for IL-12b promoter activity in an insulated chromatin environment. Mol. Cell. Biol. 27:2698–2712.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Stacey Garrett
    • 1
  • Michael C. Fitzgerald
    • 1
  • Kathleen E. Sullivan
    • 1
    • 2
  1. 1.The Division of Allergy and ImmunologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.The Division of Allergy and ImmunologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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