Journal of Clinical Immunology

, Volume 29, Issue 3, pp 257–264 | Cite as

Molecular Characterization of Human Plasmacytoid Dendritic Cells

Article

Abstract

Introduction

Plasmacytoid dendritic cells (pDCs) represent a unique and important immune cell population capable of producing large quantifies of type I interferon (IFN) in response to viruses as well as nucleic acid-containing complexes from the host. These rare and mysterious cells have been revealed by in-depth molecular characterization. Several innate sensors and signaling molecules enriched in pDCs allow their specialized innate immune functions. In addition, human pDCs use a group of surface receptors that, through activation of a B-cell receptor (BCR)-like signaling pathway, modulate type I IFN responses. It is clear now that pDC development is influenced by distinctive transcription factors that specify a unique lineage. CD4+CD56+ hematodermic neoplasm of human pDC origin has been revealed in explicit molecular terms.

Conclusion

A detailed molecular description of pDCs helps us better define, understand, and track human pDCs in relation to their functions and physiological involvement.

Keywords

Plasmacytoid dendritic cells type I interferon production regulation of interferon responses pDC development CD4+CD56+ hematodermic neoplasm 

References

  1. 1.
    Siegal FP, et al. The nature of the principal type 1 interferon-producing cells in human blood. Science 1999;284:1835–7. doi:10.1126/science.284.5421.1835.PubMedGoogle Scholar
  2. 2.
    Cella M. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce high levels of type I IFN. Nat Med. 1999;5:919–23. doi:10.1038/11360.PubMedGoogle Scholar
  3. 3.
    Liu YJ. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol. 2005;23:275–306. doi:10.1146/annurev.immunol.23.021704.115633.PubMedGoogle Scholar
  4. 4.
    Ito T, et al. Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells. Blood 2006;107:2423–31. doi:10.1182/blood-2005-07-2709.PubMedGoogle Scholar
  5. 5.
    Kadowaki N, et al. Subsets of human dendritic cell precursors express different Toll-like receptors and respond to different microbial antigens. J Exp Med. 2001;194:863–70. doi:10.1084/jem.194.6.863.PubMedGoogle Scholar
  6. 6.
    Hornung V, et al. Quantitative expression of Toll-like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol. 2002;168:4531–7.PubMedGoogle Scholar
  7. 7.
    Jarrossay D, et al. Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol. 2001;31:3388–93. doi:10.1002/1521-4141(200111)31:11<3388::AID-IMMU3388>3.0.CO;2-Q.PubMedGoogle Scholar
  8. 8.
    Colonna M, Trinchieri G, Liu YJ. Plasmacytoid dendritic cells in immunity. Nat Immunol. 2004;5:1219–26. doi:10.1038/ni1141.PubMedGoogle Scholar
  9. 9.
    Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4:499–511. doi:10.1038/nri1391.PubMedGoogle Scholar
  10. 10.
    Pasare C, Medzhitov R. Toll-like receptors: linking innate and adaptive immunity. Microbes Infect. 2004;6:1382–7. doi:10.1016/j.micinf.2004.08.018.PubMedGoogle Scholar
  11. 11.
    Lund JM, et al. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA. 2004;101:5598–603. doi:10.1073/pnas.0400937101.PubMedGoogle Scholar
  12. 12.
    Heil F, et al. Species-specific recognition of single-stranded RNA via Toll-like Receptor 7 and 8. Science 2004;303:1526–9. doi:10.1126/science.1093620.PubMedGoogle Scholar
  13. 13.
    Diebold SS, et al. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004;303:1529–31. doi:10.1126/science.1093616.PubMedGoogle Scholar
  14. 14.
    Bauer S, et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA. 2001;98:9237–42. doi:10.1073/pnas.161293498.PubMedGoogle Scholar
  15. 15.
    Hemmi H, et al. A Toll-like receptor recognizes bacterial. DNA 2000;408:740–5.Google Scholar
  16. 16.
    Haas T, et al. The DNA sugar backbone 2′ deoxyribose determines Toll-like receptor 9 Activation. Immunity 2008;28:315–23. doi:10.1016/j.immuni.2008.01.013.PubMedGoogle Scholar
  17. 17.
    Wagner H. The immunobiology of the TLR9 subfamily. Trends Immunol. 2004;25:381–6. doi:10.1016/j.it.2004.04.011.PubMedGoogle Scholar
  18. 18.
    Honda K, et al. Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc Natl Acad Sci USA. 2004;101:15416–21. doi:10.1073/pnas.0406933101.PubMedGoogle Scholar
  19. 19.
    Honda K, et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 2005;434:772–7. doi:10.1038/nature03464.PubMedGoogle Scholar
  20. 20.
    Deng L, et al. Activation of the I[kappa]B kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 2000;103:351–61. doi:10.1016/S0092-8674(00)00126-4.PubMedGoogle Scholar
  21. 21.
    Wang C, et al. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 2001;412:346–51. doi:10.1038/35085597.PubMedGoogle Scholar
  22. 22.
    Osawa Y, et al. Collaborative action of NF-{kappa}B and p38 MAPK is involved in CpG DNA-Induced IFN-{alpha} and chemokine production in human plasmacytoid dendritic cells. J Immunol. 2006;177:4841–52.PubMedGoogle Scholar
  23. 23.
    Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol. 2006;6:644–58. doi:10.1038/nri1900.PubMedGoogle Scholar
  24. 24.
    Taniguchi T, Takaoka A. The interferon-[alpha]/[beta] system in antiviral responses: a multimodal machinery of gene regulation by the IRF family of transcription factors. Curr Opin Immunol. 2002;14:111–6. doi:10.1016/S0952-7915(01)00305-3.PubMedGoogle Scholar
  25. 25.
    Colina R, et al. Translational control of the innate immune response through IRF-7. Nature 2008;452:323–8. doi:10.1038/nature06730.PubMedGoogle Scholar
  26. 26.
    Barchet W, et al. Virus-induced interferon {alpha} production by a dendritic cell subset in the absence of feedback signaling in vivo. J Exp Med. 2002;195:507–16. doi:10.1084/jem.20011666.PubMedGoogle Scholar
  27. 27.
    Tailor P, et al. The feedback phase of type i interferon induction in dendritic cells requires interferon regulatory factor 8. Immunity 2007;27:228–39. doi:10.1016/j.immuni.2007.06.009.PubMedGoogle Scholar
  28. 28.
    Tsujimura H, Tamura T, Ozato K. Cutting edge: IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type I IFN-producing plasmacytoid dendritic cells. J Immunol. 2003;170:1131–5.PubMedGoogle Scholar
  29. 29.
    Takaoka A, et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 2005;434:243–9. doi:10.1038/nature03308.PubMedGoogle Scholar
  30. 30.
    Grouard G, et al. The enigmatic plasmacytoid t cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J Exp Med. 1997;185:1101–12. doi:10.1084/jem.185.6.1101.PubMedGoogle Scholar
  31. 31.
    Latz E. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol. 2004;5:190–8.PubMedGoogle Scholar
  32. 32.
    Honda K, et al. Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 2005;434:1035–40. doi:10.1038/nature03547.PubMedGoogle Scholar
  33. 33.
    Guiducci C, et al. Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation. J Exp Med. 2006;203:1999–2008. doi:10.1084/jem.20060401.PubMedGoogle Scholar
  34. 34.
    Casrouge A, et al. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 2006;314:308–12. doi:10.1126/science.1128346.PubMedGoogle Scholar
  35. 35.
    Tabeta K, et al. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nat Immunol. 2006;7:156–64. doi:10.1038/ni1297.PubMedGoogle Scholar
  36. 36.
    Brinkmann MM, et al. The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling. J Cell Biol. 2007;177:265–75. doi:10.1083/jcb.200612056.PubMedGoogle Scholar
  37. 37.
    Yang Y, et al. Heat shock protein gp96 Is a Master Chaperone for Toll-like receptors and is important in the innate function of macrophages. Immunity 2007;26:215–26. doi:10.1016/j.immuni.2006.12.005.PubMedGoogle Scholar
  38. 38.
    Iwakoshi NN, Pypaert M, Glimcher LH. The transcription factor XBP-1 is essential for the development and survival of dendritic cells. J Exp Med 2007;204:2267–75. doi:10.1084/jem.20070525.PubMedGoogle Scholar
  39. 39.
    Birmachu W, et al. Transcriptional networks in plasmacytoid dendritic cells stimulated with synthetic TLR 7 agonists. BMC Immunol. 2007;8:26. doi:10.1186/1471-2172-8-26.PubMedGoogle Scholar
  40. 40.
    Piqueras B, et al. Upon viral exposure, myeloid and plasmacytoid dendritic cells produce 3 waves of distinct chemokines to recruit immune effectors. Blood 2006;107:2613–8. doi:10.1182/blood-2005-07-2965.PubMedGoogle Scholar
  41. 41.
    Decalf J, et al. Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients. J Exp Med. 2007;204:2423–37. doi:10.1084/jem.20070814.PubMedGoogle Scholar
  42. 42.
    Nestle FO, et al. Plasmacytoid predendritic cells initiate psoriasis through interferon-α production. J Exp Med. 2005;202:135–43. doi:10.1084/jem.20050500.PubMedGoogle Scholar
  43. 43.
    Young LJ, et al. Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells. Nat Immunol. 2008;9:1244–52. doi:10.1038/ni.1665.PubMedGoogle Scholar
  44. 44.
    Di Pucchio T, et al. Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat Immunol. 2008;9:551–7. doi:10.1038/ni.1602.PubMedGoogle Scholar
  45. 45.
    Kadowaki N, et al. Natural Interferon {alpha}/{beta}-producing Cells Link Innate and Adaptive Immunity. J Exp Med. 2000;192:219–26. doi:10.1084/jem.192.2.219.PubMedGoogle Scholar
  46. 46.
    Ito T, et al. Plasmacytoid dendritic cells regulate Th cell responses through OX40 ligand and type I IFNs. J Immunol. 2004;172:4253–9.PubMedGoogle Scholar
  47. 47.
    Ito T, et al. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J Exp Med. 2007;204:105–15. doi:10.1084/jem.20061660.PubMedGoogle Scholar
  48. 48.
    Rissoan MC, et al. Subtractive hybridization reveals the expression of immunoglobulin-like transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells. Blood 2002;100:3295–303. doi:10.1182/blood-2002–02–0638.PubMedGoogle Scholar
  49. 49.
    Stary G, et al. Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. J Exp Med. 2007;204(6):1441–51.PubMedGoogle Scholar
  50. 50.
    Chaperot L, et al. Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells. J Immunol. 2006;176:248–55.PubMedGoogle Scholar
  51. 51.
    Chen W, et al. The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J Immunol. 2008;181:5396–404.PubMedGoogle Scholar
  52. 52.
    Rissoan MC, et al. Reciprocal control of T helper cell and dendritic cell differentiation. Science 1999;283:1183–6. doi:10.1126/science.283.5405.1183.PubMedGoogle Scholar
  53. 53.
    O’Keeffe M, et al. Mouse plasmacytoid cells: long-lived cells, heterogeneous in surface phenotype and function, that differentiate into CD8 + dendritic cells only after microbial stimulus. J Exp Med. 2002;196:1307–19. doi:10.1084/jem.20021031.PubMedGoogle Scholar
  54. 54.
    Sullivan BM, Locksley RM. Basophils: a nonredundant contributor to host immunity. Immunity 2009;30:12–20. doi:10.1016/j.immuni.2008.12.006.PubMedGoogle Scholar
  55. 55.
    Cella M, et al. A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing. J Exp Med. 1997;185:1743–51. doi:10.1084/jem.185.10.1743.PubMedGoogle Scholar
  56. 56.
    Cao W, et al. Plasmacytoid dendritic cell-specific receptor ILT7-FcεRIγ inhibits Toll-like receptor-induced interferon production. J Exp Med. 2006;203:1399–405. doi:10.1084/jem.20052454.PubMedGoogle Scholar
  57. 57.
    Cella M, et al. Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. Nat Immunol. 2000;1:305–10. doi:10.1038/79747.PubMedGoogle Scholar
  58. 58.
    Dzionek A, et al. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol. 2000;165:6037–46.PubMedGoogle Scholar
  59. 59.
    Geijtenbeek TBH, et al. Self- and nonself-recognition by C-type lectins on dendritic cells. Annu Rev Immunol. 2004;22:33–54. doi:10.1146/annurev.immunol.22.012703.104558.PubMedGoogle Scholar
  60. 60.
    Cambi A, Figdor CG. Dual function of C-type lectin-like receptors in the immune system. Curr Opin Cell Biol. 2003;15:539–46. doi:10.1016/j.ceb.2003.08.004.PubMedGoogle Scholar
  61. 61.
    Steinman R, Hemmi H. Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol. 2006;311:17–58. doi:10.1007/3-540-32636-7-2.PubMedGoogle Scholar
  62. 62.
    Kanazawa N, Tashiro K, Miyachi Y. Signaling and immune regulatory role of the dendritic cell immunoreceptor (DCIR) family lectins: DCIR, DCAR, dectin-2 and BDCA-2. Immunobiology 2004;209:179–90. doi:10.1016/j.imbio.2004.03.004.PubMedGoogle Scholar
  63. 63.
    Dzionek A, et al. BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon α/β induction. J Exp Med. 2001;194:1823–34. doi:10.1084/jem.194.12.1823.PubMedGoogle Scholar
  64. 64.
    Dzionek A, et al. Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions. Hum Immunol. 2002;63:1133–48. doi:10.1016/S0198-8859(02)00752-8.PubMedGoogle Scholar
  65. 65.
    Cao W, et al. BDCA2/FcεRIγ complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. PLoS Biol. 2007;5:e248. doi:10.1371/journal.pbio.0050248.PubMedGoogle Scholar
  66. 66.
    Brown D, Trowsdale J, Allen R. The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens. 2004;64:215–25. doi:10.1111/j.0001–2815.2004.00290.x.PubMedGoogle Scholar
  67. 67.
    Ohtsuka M, et al. NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that regulates B cell development and signaling. Proc Natl Acad Sci USA. 2004;101:8126–31. doi:10.1073/pnas.0401119101.PubMedGoogle Scholar
  68. 68.
    Cho M, et al. SAGE library screening reveals ILT7 as a specific plasmacytoid dendritic cell marker that regulates type I IFN production. Int Immunol. 2008;20:155–64. doi:10.1093/intimm/dxm127.PubMedGoogle Scholar
  69. 69.
    Jun JE, Goodnow CC. Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling. Nat Immunol. 2003;4:1057–64. doi:10.1038/ni1001.PubMedGoogle Scholar
  70. 70.
    Koretzky GA, Abtahian F, Silverman MA. SLP76 and SLP65: complex regulation of signalling in lymphocytes and beyond. Nat Rev Immunol. 2006;6:67–78. doi:10.1038/nri1750.PubMedGoogle Scholar
  71. 71.
    Röck J, et al. CD303 (BDCA-2) signals in plasmacytoid dendritic cells via a BCR-like signalosome involving Syk, Slp65 and PLCγ2. Eur J Immunol. 2007;37:3564–75. doi:10.1002/eji.200737711.PubMedGoogle Scholar
  72. 72.
    Krieg AM, et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995;374:546–9. doi:10.1038/374546a0.PubMedGoogle Scholar
  73. 73.
    Novak N, et al. Characterization of FcεRI-bearing CD123 + blood dendritic cell antigen-2 + plasmacytoid dendritic cells in atopic dermatitis. J Allergy Clin Immunol. 2004;114:364–70. doi:10.1016/j.jaci.2004.05.038.PubMedGoogle Scholar
  74. 74.
    Fuchs A, et al. Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44. Blood 2005;106:2076–82. doi:10.1182/blood-2004–12–4802.PubMedGoogle Scholar
  75. 75.
    Blasius AL, et al. Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. Blood 2006;107:2474–6. doi:10.1182/blood-2005–09–3746.PubMedGoogle Scholar
  76. 76.
    Sjolin H, et al. DAP12 signaling regulates plasmacytoid dendritic cell homeostasis and down-modulates their function during viral infection. J Immunol. 2006;177:2908–16.PubMedGoogle Scholar
  77. 77.
    Lande R, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007;449:564–9. doi:10.1038/nature06116.PubMedGoogle Scholar
  78. 78.
    Blanco P, et al. Induction of dendritic cell differentiation by ifn-alpha in systemic lupus erythematosus. Science 2001;294:1540–3. doi:10.1126/science.1064890.PubMedGoogle Scholar
  79. 79.
    Marshak-Rothstein A, Rifkin IR. Immunologically active autoantigens: The role of toll-like receptors in the development of chronic inflammatory disease. Ann Rev Imm. 2007;25:419–41. doi:10.1146/annurev.immunol.22.012703.104514.Google Scholar
  80. 80.
    Yasuda K, et al. Endosomal translocation of vertebrate DNA activates dendritic cells via TLR9-dependent and -independent pathways. J Immunol. 2005;174:6129–36.PubMedGoogle Scholar
  81. 81.
    Barton GM, Kagan JC, Medzhitov R. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol. 2006;7:49–56. doi:10.1038/ni1280.PubMedGoogle Scholar
  82. 82.
    Lennert K, Kaiserling E, Müller-Hermelink H. Letter: T-associated plasma-cells. Lancet 1973;3:1031–2.Google Scholar
  83. 83.
    Muller-Hermelink H, et al. Malignant lymphoma of plasmacytoid T cells. Morphologic and immunologic studies characterizing a special type of T cell. Am J Surg Pathol. 1983;8:849–62. doi:10.1097/00000478-198307080-00013.CrossRefGoogle Scholar
  84. 84.
    Strobl H, et al. Identification of CD68 + lin- peripheral blood cells with dendritic precursor characteristics. J Immunol. 1998;161:740–8.PubMedGoogle Scholar
  85. 85.
    Liu YJ. Uncover the mystery of plasmacytoid dendritic cell precursors or type 1 interferon producing cells by serendipity. Hum Immunol. 2002;63:1067–71. doi:10.1016/S0198–8859(02)00744–9.PubMedGoogle Scholar
  86. 86.
    Onai N, et al. Identification of clonogenic common Flt3 + M-CSFR + plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat Immunol. 2007;8:1207–16. doi:10.1038/ni1518.PubMedGoogle Scholar
  87. 87.
    Naik SH, et al. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol. 2007;8:1217–26. doi:10.1038/ni1522.PubMedGoogle Scholar
  88. 88.
    Briáere F, et al. Origin and filiation of human plasmacytoid dendritic cells. Hum Immunol. 2002;63(12):1081–93. doi:10.1016/S0198-8859(02)00746-2.Google Scholar
  89. 89.
    Robbins S, et al. Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling. Genome Biol. 2008;9:R17. doi:10.1186/gb-2008-9-1-r17.PubMedGoogle Scholar
  90. 90.
    Blom B, et al. Generation of interferon {{alpha}}-producing predendritic cell (Pre-DC)2 from human CD34 + hematopoietic stem cells. J Exp Med. 2000;192:1785–96. doi:10.1084/jem.192.12.1785.PubMedGoogle Scholar
  91. 91.
    Gilliet M. The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. J Exp Med. 2002;195:953–8. doi:10.1084/jem.20020045.PubMedGoogle Scholar
  92. 92.
    Chen W, et al. Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. Blood 2004;103:2547–53. doi:10.1182/blood-2003-09-3058.PubMedGoogle Scholar
  93. 93.
    Esashi E, Wang Y-H, Perng O, Qin X-F, Liu Y-J, Watowich SS. The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8. Immunity 2008; 28(4):509–520. doi:10.1016/j.immuni.2008.02.013.Google Scholar
  94. 94.
    Lazorchak A, Jones ME, Zhuang Y. New insights into E-protein function in lymphocyte development. Trends Immunol. 2005;26:334–8. doi:10.1016/j.it.2005.03.011.PubMedGoogle Scholar
  95. 95.
    Murre C. Helix–loop–helix proteins and lymphocyte development. Nat Immunol. 2005;6:1079–86. doi:10.1038/ni1260.PubMedGoogle Scholar
  96. 96.
    Cisse B, et al. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 2008;135:37–48. doi:10.1016/j.cell.2008.09.016.PubMedGoogle Scholar
  97. 97.
    Maho Nagasawa HSMGHRSBB. Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and the Ets factor Spi-B. Eur J Immunol. 2008;38:2389–400. doi:10.1002/eji.200838470.PubMedGoogle Scholar
  98. 98.
    Julie Dwyer HLDXJPL. Transcriptional regulation of telomerase activity. Ann N Y Acad Sci. 2007;1114:36–47. doi:10.1196/annals.1396.022.PubMedGoogle Scholar
  99. 99.
    Schotte R, et al. The transcription factor Spi-B is expressed in plasmacytoid DC precursors and inhibits T-, B-, and NK-cell development. Blood 2003;101:1015–23. doi:10.1182/blood-2002-02-0438.PubMedGoogle Scholar
  100. 100.
    Schotte R, et al. The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development. J Exp Med. 2004;200:1503–9. doi:10.1084/jem.20041231.PubMedGoogle Scholar
  101. 101.
    Norton J, et al. Id helix-loop-helix proteins in cell growth and differentiation. Trends Cell Biol. 1998;8:58–65. doi:10.1016/S0962-8924(97)01183-5.PubMedGoogle Scholar
  102. 102.
    Hacker C, et al. Transcriptional profiling identifies Id2 function in dendritic cell development. Nat Immunol. 2003;4:380–6. doi:10.1038/ni903.PubMedGoogle Scholar
  103. 103.
    Spits H, et al. Id2 and Id3 inhibit development of CD34 + stem cells into predendritic cell (Pre-DC)2 but not into Pre-DC1: evidence for a lymphoid origin of Pre-DC2. J Exp Med. 2000;192:1775–84. doi:10.1084/jem.192.12.1775.PubMedGoogle Scholar
  104. 104.
    Chaperot L, et al. Identification of a leukemic counterpart of the plasmacytoid dendritic cells. Blood 2001;97:3210–7. doi:10.1182/blood.V97.10.3210.PubMedGoogle Scholar
  105. 105.
    Chaperot L, et al. Leukemic plasmacytoid dendritic cells share phenotypic and functional features with their normal counterparts. Eur J Immunol. 2004;34:418–26. doi:10.1002/eji.200324531.PubMedGoogle Scholar
  106. 106.
    Marafioti T, et al. Novel markers of normal and neoplastic human plasmacytoid dendritic cells. Blood 2008;111:3778–92. doi:10.1182/blood-2007-10-117531.PubMedGoogle Scholar
  107. 107.
    Dijkman R, et al. Gene-expression profiling and array-based CGH classify CD4 + CD56 + hematodermic neoplasm and cutaneous myelomonocytic leukemia as distinct disease entities. Blood 2007;109:1720–7. doi:10.1182/blood-2006-04-018143.PubMedGoogle Scholar
  108. 108.
    Gilliet M, Cao W, Liu YJ. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol. 2008;8:594–606. doi:10.1038/nri2358.PubMedGoogle Scholar
  109. 109.
    Kageyama R, Ohtsuka T, Kobayashi T. Roles of Hes genes in neural development. Dev Growth Differ. 2008;50(Suppl 1):S97–103.PubMedCrossRefGoogle Scholar
  110. 110.
    Swearingen ML, Sun D, Bourner M, Weinstein EJ. Detection of differentially expressed HES-6 gene in metastatic colon carcinoma by combination of suppression subtractive hybridization and cDNA library array. Cancer Lett. 2003; 198(2):229–39.Google Scholar
  111. 111.
    Gottenberg JE, et al. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjogren’s syndrome. Proc Natl Acad Sci USA. 2006;103:2770–5. doi:10.1073/pnas.0510837103.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Immunology, Unit 901, 7455 FanninThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

Personalised recommendations