Skip to main content
SpringerLink
Log in

Immunomics: At the Forefront of Innate Immunity Research

  • Chapter
  • First Online:
Clinical Applications of Immunomics

Part of the book series: Immunomics Reviews ((IMMUN,volume 2))

  • 561 Accesses

Abstract

The function and mechanisms of action of the immune system have traditionally been studied at and above the cellular level. However, due to the rapid development of molecular biology technology and widening research tool-set of genetics, as well as the success of high-throughput sequencing projects, understanding of the immune system is increasingly aided by studies performed at the molecular level. To this end, “Immunomics” is used to describe a novel field of multidisciplinary science in immunology research with the aim to derive integrated models of immune-modulatory processes.

Innate immunity is regarded as the first line of defence in fighting infections and restoring the integrity of the organism through wound healing. This chapter will focus on the recent advances in “system based” attempts to understand the molecular mechanisms of regulatory processes in innate immune responses. It will also highlight the main technologies, which have successfully been employed to identify the key components of inflammatory signal processing. We will start with introducing some of the most important “master cytokines” and cytokine receptors. We will then focus on the TIR-coupled signalling pathways induced by members of the IL-1 cytokine family, as well as by Toll-like receptors (TLR), with a brief summary of our current understanding on some crucial components in this pathway. Finally, we will discuss advanced methods for identifying novel components of important signalling pathways, highlighting the exploitation of cDNA library screen methods in innate immunity research.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aarden L A, Brunner T K, Cerrottini J C, Dayer J M, De Weck A L, Dinarello C A, Di Sabato G, Farrar J J, Gery I, Gillis S, Handschumacher R E, Henney C S, Hoffmann M K, Koopman W J, Krane S M, Lachman L B, Lefkowits I, Mishell R I, Mizel S B, Oppenheim J J, Paetkau V, Plate J, Rollinghoff M, Rosenstreich D, Rosenthal A S, Rosenwasser L J, Schimpl A, Shim H S, Simon P L, Smith K A, Wagner H, Watson J D, Wecker E, Wood D D. 1979. Revised nomenclature for antigen-non specific T cell proliferation helper factors (letter). J. Immunol. 123, 2928.

    CAS  Google Scholar 

  • Acres, R. B., Larsen, A., and Conlon, P. J. (1987). IL 1 expression in a clone of human T cells. J Immunol 138, 2132–2136.

    PubMed  CAS  Google Scholar 

  • Anderson, K. V., Bokla, L., and Nusslein-Volhard, C. (1985a). Establishment of dorsal-ventral polarity in the Drosophila embryo: The induction of polarity by the Toll gene product. Cell 42, 791–798.

    Google Scholar 

  • Anderson, K. V., Jurgens, G., and Nusslein-Volhard, C. (1985b). Establishment of dorsal-ventral polarity in the Drosophila embryo: Genetic studies on the role of the Toll gene product. Cell 42, 779–789.

    Google Scholar 

  • Aruffo, A., and Seed, B. (1987). Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A 84, 8573–8577.

    Google Scholar 

  • Auron, P. E., Webb, A. C., Rosenwasser, L. J., Mucci, S. F., Rich, A., Wolff, S. M., and Dinarello, C. A. (1984). Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A 81, 7907– 7911.

    Google Scholar 

  • Baker, B., Zambryski, P., Staskawicz, B., and Dinesh-Kumar, S. P. (1997). Signaling in plant-microbe interactions. Science 276, 726–733.

    Article  PubMed  CAS  Google Scholar 

  • Barksby, H. E., Lea, S. R., Preshaw, P. M., and Taylor, J. J. (2007). The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders. Clin Exp Immunol 149, 217–225.

    Article  PubMed  CAS  Google Scholar 

  • Bent, A. F. (1996). Plant Disease Resistance Genes: Function Meets Structure. Plant Cell 8, 1757–1771.

    Article  PubMed  CAS  Google Scholar 

  • Beutler, B., Du, X., and Hoebe, K. (2003). From phenomenon to phenotype and from phenotype to gene: Forward genetics and the problem of sepsis. J Infect Dis187 Suppl 2, S321–326.

    Article  Google Scholar 

  • Beutler, B., and Rehli, M. (2002). Evolution of the TIR, tolls and TLRs: Functional inferences from computational biology. Curr Top Microbiol Immunol 270, 1–21.

    Article  PubMed  CAS  Google Scholar 

  • Biron, C. A. (2001). Interferons alpha and beta as immune regulators – a new look. Immunity 14, 661–664.

    Article  PubMed  CAS  Google Scholar 

  • Bonizzi, G., and Karin, M. (2004). The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25, 280–288.

    Article  PubMed  CAS  Google Scholar 

  • Born, T. L., Thomassen, E., Bird, T. A., and Sims, J. E. (1998). Cloning of a novel receptor subunit, AcPL, required for interleukin-18 signaling. J Biol Chem 273, 29445–29450.

    Google Scholar 

  • Bright, S. W., Chen, T. Y., Flebbe, L. M., Lei, M. G., and Morrison, D. C. (1990). Generation and characterization of hamster-mouse hybridomas secreting monoclonal antibodies with specificity for lipopolysaccharide receptor. J Immunol 145, 1–7.

    PubMed  CAS  Google Scholar 

  • Burns, K., Martinon, F., Esslinger, C., Pahl, H., Schneider, P., Bodmer, J. L., Di Marco, F., French, L., and Tschopp, J. (1998). MyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem 273, 12203–12209.

    Google Scholar 

  • Cao, Z., Henzel, W. J., and Gao, X. (1996). IRAK: A kinase associated with the interleukin-1 receptor. Science 271, 1128–1131.

    Article  PubMed  CAS  Google Scholar 

  • Chanda, S. K., White, S., Orth, A. P., Reisdorph, R., Miraglia, L., Thomas, R. S., DeJesus, P., Mason, D. E., Huang, Q., Vega, R., et al (2003). Genome-scale functional profiling of the mammalian AP-1 signaling pathway. Proc Natl Acad Sci U S A 100, 12153–12158.

    Google Scholar 

  • Chantry, D., Turner, M., Abney, E., and Feldmann, M. (1989). Modulation of cytokine production by transforming growth factor-beta. J Immunol 142, 4295–4300.

    PubMed  CAS  Google Scholar 

  • Chen, R., Alvero, A. B., Silasi, D. A., and Mor, G. (2007). Inflammation, cancer and chemoresistance: Taking advantage of the toll-like receptor signaling pathway. Am J Reprod Immunol 57, 93–107.

    Article  PubMed  CAS  Google Scholar 

  • Chen, T. Y., Bright, S. W., Pace, J. L., Russell, S. W., and Morrison, D. C. (1990). Induction of macrophage-mediated tumor cytotoxicity by a hamster monoclonal antibody with specificity for lipopolysaccharide receptor. J Immunol 145, 8–12.

    PubMed  CAS  Google Scholar 

  • Chen, Z. J., Parent, L., and Maniatis, T. (1996). Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity. Cell 84, 853–862.

    Article  PubMed  CAS  Google Scholar 

  • Coutinho, A., Forni, L., Melchers, F., and Watanabe, T. (1977). Genetic defect in responsiveness to the B cell mitogen lipopolysaccharide. Eur J Immunol 7, 325–328.

    Article  PubMed  CAS  Google Scholar 

  • de Waal Malefyt, R., Abrams, J., Bennett, B., Figdor, C. G., and de Vries, J. E. (1991). Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes. J Exp Med 174, 1209–1220.

    Article  PubMed  Google Scholar 

  • Deng, T., and Karin, M. (1994). c-Fos transcriptional activity stimulated by H-Ras-activated protein kinase distinct from JNK and ERK. Nature 371, 171–175.

    Article  PubMed  CAS  Google Scholar 

  • Eisenberg, S. P., Evans, R. J., Arend, W. P., Verderber, E., Brewer, M. T., Hannum, C. H., and Thompson, R. C. (1990). Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature 343, 341–346.

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald, K. A., Rowe, D. C., Barnes, B. J., Caffrey, D. R., Visintin, A., Latz, E., Monks, B., Pitha, P. M., and Golenbock, D. T. (2003). LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J Exp Med 198, 1043–1055.

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald, K. A., Palsson-McDermott, E. M., Bowie, A. G., Jefferies, C. A., Mansell, A. S., Brady, G., Brint, E., Dunne, A., Gray, P., Harte, M. T., et al (2001). Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413, 78–83.

    Article  PubMed  CAS  Google Scholar 

  • Galindo, R. L., Edwards, D. N., Gillespie, S. K., and Wasserman, S. A. (1995). Interaction of the pelle kinase with the membrane-associated protein tube is required for transduction of the dorsoventral signal in Drosophila embryos. Development 121, 2209–2218.

    PubMed  CAS  Google Scholar 

  • Gay, N. J., and Keith, F. J. (1991). Drosophila Toll and IL-1 receptor. Nature 351, 355–356.

    Article  PubMed  CAS  Google Scholar 

  • Gerttula, S., Jin, Y. S., and Anderson, K. V. (1988). Zygotic expression and activity of the Drosophila Toll gene, a gene required maternally for embryonic dorsal-ventral pattern formation. Genetics 119, 123–133.

    PubMed  CAS  Google Scholar 

  • Glode, L. M., and Rosenstreich, D. L. (1976). Genetic control of B cell activation by bacterial lipopolysaccharide is mediated by multiple distinct genes or alleles. J Immunol 117, 2061–2066.

    PubMed  CAS  Google Scholar 

  • Greenfeder, S. A., Nunes, P., Kwee, L., Labow, M., Chizzonite, R. A., and Ju, G. (1995). Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J Biol Chem 270, 13757–13765.

    Google Scholar 

  • Grosshans, J., Bergmann, A., Haffter, P., and Nusslein-Volhard, C. (1994). Activation of the kinase Pelle by Tube in the dorsoventral signal transduction pathway of Drosophila embryo. Nature 372, 563–566.

    Article  PubMed  CAS  Google Scholar 

  • Guan, H., Holland, K., Qwarnstrom, E., Dower, S. K., and Kiss-Toth, E. (2006). Feedback loops in intracellular signal processing and their potential for identifying novel signalling proteins. Cell Immunol 244, 158–161.

    Article  PubMed  CAS  Google Scholar 

  • Guan, H., Kiss-toth, E., and Dower, SK. (2007). Analysis of innate immune signal transduction with autocatalytic expression vectors. Journal of Immunological Methods. 330(1–2), 96–108. Doi: 10.1016/j.jim.2007.11.002

    Google Scholar 

  • Gubler, U., Chua, A. O., Stern, A. S., Hellmann, C. P., Vitek, M. P., DeChiara, T. M., Benjamin, W. R., Collier, K. J., Dukovich, M., Familletti, P. C., and et al. (1986). Recombinant human interleukin 1 alpha: Purification and biological characterization. J Immunol 136, 2492–2497.

    PubMed  CAS  Google Scholar 

  • Hayden, M. S., and Ghosh, S. (2004). Signaling to NF-kappaB. Genes Dev 18, 2195–2224.

    Article  PubMed  CAS  Google Scholar 

  • Horng, T., Barton, G. M., and Medzhitov, R. (2001). TIRAP: An adapter molecule in the Toll signaling pathway. Nat Immunol 2, 835–841.

    Article  PubMed  CAS  Google Scholar 

  • Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., and Akira, S. (1999). Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: Evidence for TLR4 as the Lps gene product. J Immunol 162, 3749–3752.

    PubMed  CAS  Google Scholar 

  • Huang, Y., Li, T., Sane, D. C., and Li, L. (2004). IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced interleukin-10 gene expression. J Biol Chem 279, 51697–51703.

    Google Scholar 

  • Huang, Y. S., Misior, A., and Li, L. W. (2005). Novel role and regulation of the interleukin-1 receptor associated kinase (IRAK) family proteins. Cell Mol Immunol 2, 36–39.

    PubMed  CAS  Google Scholar 

  • Iourgenko, V., Zhang, W., Mickanin, C., Daly, I., Jiang, C., Hexham, J. M., Orth, A. P., Miraglia, L., Meltzer, J., Garza, D., Chirn, G. W., McWhinnie, E., Cohen, D., Skelton, J., Terry, R., Yu, Y., Bodian, D., Buxton, F. P., Zhu, J., Song, C., and Labow, M. A. (2003). Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells. Proc Natl Acad Sci U S A 100, 12147–12152.

    Google Scholar 

  • Isaacs, A., and Lindenmann, J. (1957). Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 147, 258–267.

    Google Scholar 

  • Isaacs, A., Lindenmann, J., and Valentine, R. C. (1957). Virus interference. II. Some properties of interferon. Proc R Soc Lond B Biol Sci 147, 268–273.

    Google Scholar 

  • John, J., McKendry, R., Pellegrini, S., Flavell, D., Kerr, I. M., and Stark, G. R. (1991). Isolation and characterization of a new mutant human cell line unresponsive to alpha and beta interferons. Mol Cell Biol 11, 4189–4195.

    PubMed  CAS  Google Scholar 

  • Kiss-Toth, E., Guesdon, F. M., Wyllie, D. H., Qwarnstrom, E. E., and Dower, S. K. (2000). A novel mammalian expression screen exploiting green fluorescent protein-based transcription detection in single cells. J Immunol Methods 239, 125–135.

    Article  PubMed  CAS  Google Scholar 

  • Kiss-Toth, E., Qwarnstrom, E. E., and Dower, S. K. (2004). Hunting for genes by functional screens. Cytokine Growth Factor Rev 15, 97–102.

    Article  PubMed  CAS  Google Scholar 

  • Kiss-Toth, E., Wyllie, D. H., Holland, K., Marsden, L., Jozsa, V., Oxley, K. M., Polgar, T., Qwarnstrom, E. E., and Dower, S. K. (2006). Functional mapping and identification of novel regulators for the Toll/Interleukin-1 signalling network by transcription expression cloning. Cell Signal 18, 202–214.

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi, K., Hernandez, L. D., Galan, J. E., Janeway, C. A., Jr., Medzhitov, R., and Flavell, R. A. (2002). IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110, 191–202.

    Article  PubMed  CAS  Google Scholar 

  • Lee, F. S., Peters, R. T., Dang, L. C., and Maniatis, T. (1998). MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta. Proc Natl Acad Sci U S A 95, 9319–9324.

    Google Scholar 

  • Lee, N. K., and Lee, S. Y. (2002). Modulation of life and death by the tumor necrosis factor receptor-associated factors (TRAFs). J Biochem Mol Biol 35, 61–66.

    Article  PubMed  Google Scholar 

  • Lei, M. G., and Morrison, D. C. (1988a). Specific endotoxic lipopolysaccharide-binding proteins on murine splenocytes. I. Detection of lipopolysaccharide-binding sites on splenocytes and splenocyte subpopulations. J Immunol 141, 996–1005.

    Google Scholar 

  • Lei, M. G., and Morrison, D. C. (1988b). Specific endotoxic lipopolysaccharide-binding proteins on murine splenocytes. II. Membrane localization and binding characteristics. J Immunol 141, 1006–1011.

    Google Scholar 

  • Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J. M., and Hoffmann, J. A. (1996). The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973–983.

    Article  PubMed  CAS  Google Scholar 

  • Li, S., Strelow, A., Fontana, E. J., and Wesche, H. (2002). IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase. Proc Natl Acad Sci U S A 99, 5567–5572.

    Google Scholar 

  • Li, X., Commane, M., Jiang, Z., and Stark, G. R. (2001). IL-1-induced NFkappa B and c-Jun N-terminal kinase (JNK) activation diverge at IL-1 receptor-associated kinase (IRAK). Proc Natl Acad Sci U S A 98, 4461–4465.

    Google Scholar 

  • Lomedico, P. T., Gubler, U., Hellmann, C. P., Dukovich, M., Giri, J. G., Pan, Y. C., Collier, K., Semionow, R., Chua, A. O., and Mizel, S. B. (1984). Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature 312, 458–462.

    Article  PubMed  CAS  Google Scholar 

  • Lord, K. A., Hoffman-Liebermann, B., and Liebermann, D. A. (1990). Nucleotide sequence and expression of a cDNA encoding MyD88, a novel myeloid differentiation primary response gene induced by IL6. Oncogene 5, 1095–1097.

    PubMed  CAS  Google Scholar 

  • Lutfalla, G., Holland, S. J., Cinato, E., Monneron, D., Reboul, J., Rogers, N. C., Smith, J. M., Stark, G. R., Gardiner, K., Mogensen, K. E., and et al. (1995). Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit generated by alternative processing of a new member of a cytokine receptor gene cluster. Embo J 14, 5100–5108.

    PubMed  CAS  Google Scholar 

  • March, C. J., Mosley, B., Larsen, A., Cerretti, D. P., Braedt, G., Price, V., Gillis, S., Henney, C. S., Kronheim, S. R., Grabstein, K., and et al. (1985). Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 315, 641–647.

    Article  PubMed  CAS  Google Scholar 

  • McKendry, R., John, J., Flavell, D., Muller, M., Kerr, I. M., and Stark, G. R. (1991). High-frequency mutagenesis of human cells and characterization of a mutant unresponsive to both alpha and gamma interferons. Proc Natl Acad Sci U S A 88, 11455–11459.

    Google Scholar 

  • McMahan, C. J., Slack, J. L., Mosley, B., Cosman, D., Lupton, S. D., Brunton, L. L., Grubin, C. E., Wignall, J. M., Jenkins, N. A., Brannan, C. I., and et al. (1991). A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. Embo J 10, 2821–2832.

    PubMed  CAS  Google Scholar 

  • Medzhitov, R., Preston-Hurlburt, P., and Janeway, C. A., Jr. (1997). A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394–397.

    Article  PubMed  CAS  Google Scholar 

  • Medzhitov, R., Preston-Hurlburt, P., Kopp, E., Stadlen, A., Chen, C., Ghosh, S., and Janeway, C. A., Jr. (1998). MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol Cell 2, 253–258.

    Article  PubMed  CAS  Google Scholar 

  • Mercurio, F., Zhu, H., Murray, B. W., Shevchenko, A., Bennett, B. L., Li, J., Young, D. B., Barbosa, M., Mann, M., Manning, A., and Rao, A. (1997). IKK-1 and IKK-2: Cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 278, 860–866.

    Article  PubMed  CAS  Google Scholar 

  • Morrison, D. C., and Ryan, J. L. (1979). Bacterial endotoxins and host immune responses. Adv Immunol 28, 293–450.

    Article  PubMed  CAS  Google Scholar 

  • Muzio, M., Ni, J., Feng, P., and Dixit, V. M. (1997). IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278, 1612–1615.

    Article  PubMed  CAS  Google Scholar 

  • O'Neill, L. A. (1995). Towards an understanding of the signal transduction pathways for interleukin 1. Biochim Biophys Acta 1266, 31–44.

    Article  PubMed  Google Scholar 

  • Osborne, M. A., Dalton, S., and Kochan, J. P. (1995). The yeast tribrid system – genetic detection of trans-phosphorylated ITAM-SH2-interactions. Biotechnology (N Y) 13, 1474–1478.

    Article  CAS  Google Scholar 

  • Parnet, P., Garka, K. E., Bonnert, T. P., Dower, S. K., and Sims, J. E. (1996). IL-1Rrp is a novel receptor-like molecule similar to the type I interleukin-1 receptor and its homologues T1/ST2 and IL-1R AcP. J Biol Chem 271, 3967–3970.

    Article  PubMed  CAS  Google Scholar 

  • Peiffer-Schneider, S., Schutte, B. C., Murray, J. C., Frees, K. L., Williamson, K., Leysens, N. J., and Schwartz, D. A. (1997). Exclusion of Ifa and Ifb as the Lps gene and mapping of three markers near the Lps locus. Mamm Genome 8, 785–786.

    Article  PubMed  CAS  Google Scholar 

  • Perkins, N. D. (2007). Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8, 49–62.

    Article  PubMed  CAS  Google Scholar 

  • Peters, R. T., and Maniatis, T. (2001). A new family of IKK-related kinases may function as I kappa B kinase kinases. Biochim Biophys Acta 1471, M57–62.

    Google Scholar 

  • Poltorak, A., He, X., Smirnova, I., Liu, M. Y., Van Huffel, C., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998a). Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene. Science 282, 2085–2088.

    Google Scholar 

  • Poltorak, A., Smirnova, I., He, X., Liu, M. Y., Van Huffel, C., McNally, O., Birdwell, D., Alejos, E., Silva, M., Du, X., et al. (1998b). Genetic and physical mapping of the Lps locus: Identification of the toll-4 receptor as a candidate gene in the critical region. Blood Cells Mol Dis 24, 340–355.

    Google Scholar 

  • Qureshi, S. T., Lariviere, L., Leveque, G., Clermont, S., Moore, K. J., Gros, P., and Malo, D. (1999). Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J Exp Med 189, 615–625.

    Article  PubMed  CAS  Google Scholar 

  • Qureshi, S. T., Lariviere, L., Sebastiani, G., Clermont, S., Skamene, E., Gros, P., and Malo, D. (1996). A high-resolution map in the chromosomal region surrounding the Lps locus. Genomics 31, 283–294.

    Article  PubMed  CAS  Google Scholar 

  • Remy, I., and Michnick, S. W. (2004). A cDNA library functional screening strategy based on fluorescent protein complementation assays to identify novel components of signaling pathways. Methods 32, 381–388.

    Article  PubMed  CAS  Google Scholar 

  • Rock, F. L., Hardiman, G., Timans, J. C., Kastelein, R. A., and Bazan, J. F. (1998). A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A 95, 588–593.

    Google Scholar 

  • Rodriguez, A., Vigorito, E., Clare, S., Warren, M. V., Couttet, P., Soond, D. R., van Dongen, S., Grocock, R. J., Das, P. P., Miska, E. A., et al. (2007). Requirement of bic/microRNA-155 for normal immune function. Science 316, 608–611.

    Article  PubMed  CAS  Google Scholar 

  • Rothe, M., Wong, S. C., Henzel, W. J., and Goeddel, D. V. (1994). A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 78, 681–692.

    Article  PubMed  CAS  Google Scholar 

  • Roux-Lombard, P. (1998). The interleukin-1 family. Eur Cytokine Netw 9, 565–576.

    PubMed  CAS  Google Scholar 

  • Schindler, R., Mancilla, J., Endres, S., Ghorbani, R., Clark, S. C., and Dinarello, C. A. (1990). Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood 75, 40–47.

    PubMed  CAS  Google Scholar 

  • Schmitz, J., Owyang, A., Oldham, E., Song, Y., Murphy, E., McClanahan, T. K., Zurawski, G., Moshrefi, M., Qin, J., Li, X., et al. (2005). IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23, 479–490.

    Article  PubMed  CAS  Google Scholar 

  • Schonbach, C. (2003). From immunogenetics to immunomics: Functional prospecting of genes and transcripts. Novartis Found Symp 254, 177–188; discussion 189–192, 216–122, 250–172.

    Article  PubMed  CAS  Google Scholar 

  • Scibienski, R. J. (1981). Immunologic properties of protein-lipopolysaccharide complexes. IV. Circumventing suppression in immunologically tolerant animals. Cell Immunol 58, 293–301.

    Article  PubMed  CAS  Google Scholar 

  • Shibuya, H., Yamaguchi, K., Shirakabe, K., Tonegawa, A., Gotoh, Y., Ueno, N., Irie, K., Nishida, E., and Matsumoto, K. (1996). TAB1: An activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science 272, 1179–1182.

    Article  PubMed  CAS  Google Scholar 

  • Shirakawa, F., Saito, K., Bonagura, C. A., Galson, D. L., Fenton, M. J., Webb, A. C., and Auron, P. E. (1993). The human prointerleukin 1 beta gene requires DNA sequences both proximal and distal to the transcription start site for tissue-specific induction. Mol Cell Biol 13, 1332–1344.

    PubMed  CAS  Google Scholar 

  • Sims, J. E., Acres, R. B., Grubin, C. E., McMahan, C. J., Wignall, J. M., March, C. J., and Dower, S. K. (1989). Cloning the interleukin 1 receptor from human T cells. Proc Natl Acad Sci U S A 86, 8946–8950.

    Google Scholar 

  • Sims, J. E., Giri, J. G., and Dower, S. K. (1994). The two interleukin-1 receptors play different roles in IL-1 actions. Clin Immunol Immunopathol 72, 9–14.

    Article  PubMed  CAS  Google Scholar 

  • Sims, J. E., March, C. J., Cosman, D., Widmer, M. B., MacDonald, H. R., McMahan, C. J., Grubin, C. E., Wignall, J. M., Jackson, J. L., Call, S. M., and et al. (1988). cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Science 241, 585–589.

    Article  PubMed  CAS  Google Scholar 

  • Sims, J. E., Nicklin, M. J., Bazan, J. F., Barton, J. L., Busfield, S. J., Ford, J. E., Kastelein, R. A., Kumar, S., Lin, H., Mulero, J. J., et al. (2001). A new nomenclature for IL-1-family genes. Trends Immunol 22, 536–537.

    Article  PubMed  CAS  Google Scholar 

  • Sreekumar, A., Nyati, M. K., Varambally, S., Barrette, T. R., Ghosh, D., Lawrence, T. S., and Chinnaiyan, A. M. (2001). Profiling of cancer cells using protein microarrays: Discovery of novel radiation-regulated proteins. Cancer Res 61, 7585–7593.

    PubMed  CAS  Google Scholar 

  • Stark, G. R., Kerr, I. M., Williams, B. R., Silverman, R. H., and Schreiber, R. D. (1998). How cells respond to interferons. Annu Rev Biochem 67, 227–264.

    Article  PubMed  CAS  Google Scholar 

  • Sultzer, B. M. (1968). Genetic control of leucocyte responses to endotoxin. Nature 219, 1253–1254.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki, N., Suzuki, S., Duncan, G. S., Millar, D. G., Wada, T., Mirtsos, C., Takada, H., Wakeham, A., Itie, A., Li, S., et al. (2002). Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature 416, 750–756.

    Article  PubMed  CAS  Google Scholar 

  • Swantek, J. L., Tsen, M. F., Cobb, M. H., and Thomas, J. A. (2000). IL-1 receptor-associated kinase modulates host responsiveness to endotoxin. J Immunol 164, 4301–4306.

    PubMed  CAS  Google Scholar 

  • Symons, J. A., Eastgate, J. A., and Duff, G. W. (1991). Purification and characterization of a novel soluble receptor for interleukin 1. J Exp Med 174, 1251–1254.

    Article  PubMed  CAS  Google Scholar 

  • Theofilopoulos, A. N., Baccala, R., Beutler, B., and Kono, D. H. (2005). Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev Immunol 23, 307–336.

    Article  PubMed  CAS  Google Scholar 

  • Tojima, Y., Fujimoto, A., Delhase, M., Chen, Y., Hatakeyama, S., Nakayama, K., Kaneko, Y., Nimura, Y., Motoyama, N., Ikeda, K., et al. (2000). NAK is an IkappaB kinase-activating kinase. Nature 404, 778–782.

    Article  PubMed  CAS  Google Scholar 

  • Toshchakov, V., Jones, B. W., Perera, P. Y., Thomas, K., Cody, M. J., Zhang, S., Williams, B. R., Major, J., Hamilton, T. A., Fenton, M. J., and Vogel, S. N. (2002). TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages. Nat Immunol 3, 392–398.

    Article  PubMed  CAS  Google Scholar 

  • Towne, J. E., Garka, K. E., Renshaw, B. R., Virca, G. D., and Sims, J. E. (2004). Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. J Biol Chem 279, 13677–13688.

    Article  Google Scholar 

  • Tsukada, J., Saito, K., Waterman, W. R., Webb, A. C., and Auron, P. E. (1994). Transcription factors NF-IL6 and CREB recognize a common essential site in the human prointerleukin 1 beta gene. Mol Cell Biol 14, 7285–7297.

    PubMed  CAS  Google Scholar 

  • Uze, G., Lutfalla, G., and Gresser, I. (1990). Genetic transfer of a functional human interferon alpha receptor into mouse cells: Cloning and expression of its cDNA. Cell 60, 225–234.

    Article  PubMed  CAS  Google Scholar 

  • van Boxel-Dezaire, A. H., Rani, M. R., and Stark, G. R. (2006). Complex modulation of cell type-specific signaling in response to type I interferons. Immunity 25, 361–372.

    Article  PubMed  Google Scholar 

  • Vannier, E., Miller, L. C., and Dinarello, C. A. (1992). Coordinated antiinflammatory effects of interleukin 4: Interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist. Proc Natl Acad Sci U S A 89, 4076–4080.

    Google Scholar 

  • Watson, J., Kelly, K., Largen, M., and Taylor, B. A. (1978). The genetic mapping of a defective LPS response gene in C3H/HeJ mice. J Immunol 120, 422–424.

    PubMed  CAS  Google Scholar 

  • Watson, J., and Riblet, R. (1974). Genetic control of responses to bacterial lipopolysaccharides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic respones to lipopolysaccharides. J Exp Med 140, 1147–1161.

    Article  PubMed  CAS  Google Scholar 

  • Wesche, H., Gao, X., Li, X., Kirschning, C. J., Stark, G. R., and Cao, Z. (1999). IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 274, 19403–19410.

    Google Scholar 

  • Williams, M. J., Rodriguez, A., Kimbrell, D. A., and Eldon, E. D. (1997). The 18-wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense. Embo J 16, 6120–6130.

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi, K., Shirakabe, K., Shibuya, H., Irie, K., Oishi, I., Ueno, N., Taniguchi, T., Nishida, E., and Matsumoto, K. (1995). Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science 270, 2008–2011.

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto, M., Sato, S., Mori, K., Hoshino, K., Takeuchi, O., Takeda, K., and Akira, S. (2002). Cutting edge: A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 169, 6668–6672.

    PubMed  CAS  Google Scholar 

  • Yates, L. L., and Gorecki, D. C. (2006). The nuclear factor-kappaB (NF-kappaB): From a versatile transcription factor to a ubiquitous therapeutic target. Acta Biochim Pol 53, 651–662.

    PubMed  CAS  Google Scholar 

  • Zandi, E., Rothwarf, D. M., Delhase, M., Hayakawa, M., and Karin, M. (1997). The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell 91, 243–252.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiovascular Research Unit, University of Sheffield, Royal Hallamshire Hospital, Glossop road, Sheffield, S10 2JF, UK

    Endre Kiss-Toth

Authors
  1. Hongtao Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steven K Dower
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Endre Kiss-Toth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Endre Kiss-Toth .

Editor information

Editors and Affiliations

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2009 Springer Science+Business Media, LLC

    About this chapter

    Cite this chapter

    Guan, H., Dower, S.K., Kiss-Toth, E. (2009). Immunomics: At the Forefront of Innate Immunity Research. In: Falus, A. (eds) Clinical Applications of Immunomics. Immunomics Reviews, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-0-387-79208-8_2

    Download citation

    Publish with us

    Policies and ethics

    Search

    Navigation