Home LiteratureArticle Details
PMID: 11602640 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells.

The Journal of experimental medicine ·Vol. 194 ·No. 8 ·2001-10-15 ·Pages 1111-22

Bouchon A, Hernández-Munain C, Cella M, Colonna M

Abstract

Gene targeting of the adaptor molecule DAP12 in mice caused abnormal distribution and impaired antigen presentation capacity of dendritic cells (DCs). However, the DAP12-associated receptors expressed on DCs and their functions have not been identified yet. Here we show that the triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12. TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase. In contrast to Toll-like receptor-mediated signaling, TREM2/DAP12 stimulation is independent of nuclear factor-kappaB and p38 stress-activated protein kinase. This novel DC activation pathway may regulate DC homeostasis and amplify DC responses to pathogens, explaining the phenotype observed in DAP12-deficient mice.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Antigens, CD/biosynthesis B7-2 Antigen CD40 Antigens/biosynthesis Cell Differentiation Cell Line Cell Survival DNA-Binding Proteins/metabolism Dendritic Cells/cytology,drug effects,metabolism Enzyme Activation Hematopoietic Stem Cells/cytology,metabolism Histocompatibility Antigens Class II/biosynthesis Humans I-kappa B Proteins Membrane Glycoproteins/biosynthesis,genetics,metabolism Membrane Proteins Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases/antagonists & inhibitors,metabolism Monocytes/cytology,metabolism NF-KappaB Inhibitor alpha NF-kappa B/antagonists & inhibitors,metabolism Protein-Tyrosine Kinases/antagonists & inhibitors Receptors, CCR7 Receptors, Chemokine/biosynthesis,genetics Receptors, Immunologic/genetics,metabolism Signal Transduction/physiology Triggering Receptor Expressed on Myeloid Cells-1 Up-Regulation p38 Mitogen-Activated Protein Kinases
Chemicals
Adaptor Proteins, Signal Transducing Antigens, CD B7-2 Antigen CCR7 protein, human CD40 Antigens CD86 protein, human Ccr7 protein, mouse Cd86 protein, mouse DNA-Binding Proteins Histocompatibility Antigens Class II I-kappa B Proteins Membrane Glycoproteins Membrane Proteins NF-kappa B NFKBIA protein, human Nfkbia protein, mouse Receptors, CCR7 Receptors, Chemokine Receptors, Immunologic TREM1 protein, human TREM2 protein, human TYROBP protein, human Trem2 protein, mouse Triggering Receptor Expressed on Myeloid Cells-1 NF-KappaB Inhibitor alpha Protein-Tyrosine Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bouchon A
Basel Institute for Immunology, CH-4005 Basel, Switzerland.
Hernández-Munain C
Cella M
Colonna M
References (88)
88 references, click to expand
  1. A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4.
    Blood. 1998 Apr 15;91(8):2886-95 PMID: 9531599
  2. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.
    Annu Rev Immunol. 1998;16:225-60 PMID: 9597130
  3. Immunology. Licence to kill.
    Nature. 1998 Jun 4;393(6684):413-4 PMID: 9623994
  4. Dissociation of cytokine-induced phosphorylation of Bad and activation of PKB/akt: involvement of MEK upstream of Bad phosphorylation.
    Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7439-44 PMID: 9636168
  5. Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors.
    J Immunol. 1998 Jul 1;161(1):7-10 PMID: 9647200
  6. Association of DAP12 with activating CD94/NKG2C NK cell receptors.
    Immunity. 1998 Jun;8(6):693-701 PMID: 9655483
  7. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites.
    J Exp Med. 1998 Jul 20;188(2):373-86 PMID: 9670049
  8. Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties.
    J Immunol. 1998 Aug 1;161(3):1083-6 PMID: 9686565
  9. syk protein tyrosine kinase regulates Fc receptor gamma-chain-mediated transport to lysosomes.
    EMBO J. 1998 Aug 17;17(16):4606-16 PMID: 9707420
  10. The Bcl-2 protein family: arbiters of cell survival.
    Science. 1998 Aug 28;281(5381):1322-6 PMID: 9735050
  11. EBI1/CCR7 is a new member of dendritic cell chemokine receptor that is up-regulated upon maturation.
    J Immunol. 1998 Sep 15;161(6):3096-102 PMID: 9743376
  12. Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation.
    Eur J Immunol. 1998 Sep;28(9):2760-9 PMID: 9754563
  13. DAP12-mediated signal transduction in natural killer cells. A dominant role for the Syk protein-tyrosine kinase.
    J Biol Chem. 1998 Dec 4;273(49):32934-42 PMID: 9830044
  14. Dendritic cell survival and maturation are regulated by different signaling pathways.
    J Exp Med. 1998 Dec 7;188(11):2175-80 PMID: 9841930
  15. Gene structure, expression pattern, and biological activity of mouse killer cell activating receptor-associated protein (KARAP)/DAP-12.
    J Biol Chem. 1998 Dec 18;273(51):34115-9 PMID: 9852069
  16. Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression.
    Genes Dev. 1995 Aug 15;9(16):1965-77 PMID: 7649478
  17. Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells.
    Eur J Immunol. 1996 Mar;26(3):659-68 PMID: 8605935
  18. 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 Aug 1;184(2):741-6 PMID: 8760828
  19. 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 Aug 1;184(2):747-52 PMID: 8760829
  20. Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood.
    J Immunol Methods. 1996 Sep 27;196(2):121-35 PMID: 8841451
  21. A family of proteins that inhibit signalling through tyrosine kinase receptors.
    Nature. 1997 Mar 13;386(6621):181-6 PMID: 9062191
  22. NF-kappa B RelA-deficient lymphocytes: normal development of T cells and B cells, impaired production of IgA and IgG1 and reduced proliferative responses.
    J Exp Med. 1997 Mar 3;185(5):953-61 PMID: 9120401
  23. Human killer cell activatory receptors for MHC class I molecules are included in a multimeric complex expressed by natural killer cells.
    J Immunol. 1997 Jun 1;158(11):5083-6 PMID: 9164921
  24. Interleukin-18 activates NF-kappaB in murine T helper type 1 cells.
    Biochem Biophys Res Commun. 1997 May 19;234(2):454-7 PMID: 9177292
  25. IkappaB-NF-kappaB structures: at the interface of inflammation control.
    Cell. 1998 Dec 11;95(6):729-31 PMID: 9865689
  26. Human myeloid cells express an activating ILT receptor (ILT1) that associates with Fc receptor gamma-chain.
    J Immunol. 1999 Jan 1;162(1):5-8 PMID: 9886363
  27. Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization.
    J Exp Med. 1999 Jan 18;189(2):371-80 PMID: 9892619
  28. Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen.
    J Exp Med. 1999 Jan 18;189(2):403-12 PMID: 9892622
  29. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization.
    J Exp Med. 1999 Feb 1;189(3):451-60 PMID: 9927507
  30. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis.
    Nature. 1999 Jan 28;397(6717):315-23 PMID: 9950424
  31. NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily.
    J Exp Med. 1999 Mar 1;189(5):787-96 PMID: 10049942
  32. Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes.
    J Immunol. 1999 Mar 1;162(5):2472-5 PMID: 10072485
  33. TRANCE, a tumor necrosis factor family member critical for CD40 ligand-independent T helper cell activation.
    J Exp Med. 1999 Apr 5;189(7):1025-31 PMID: 10190893
  34. An activating immunoreceptor complex formed by NKG2D and DAP10.
    Science. 1999 Jul 30;285(5428):730-2 PMID: 10426994
  35. BCL-2 family members and the mitochondria in apoptosis.
    Genes Dev. 1999 Aug 1;13(15):1899-911 PMID: 10444588
  36. Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells.
    Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9792-6 PMID: 10449773
  37. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.
    Cell. 1999 Oct 1;99(1):23-33 PMID: 10520991
  38. Regulation of bad phosphorylation and association with Bcl-x(L) by the MAPK/Erk kinase.
    J Biol Chem. 1999 Oct 22;274(43):31108-13 PMID: 10521512
  39. Cloning and characterization of a novel activating Ly49 closely related to Ly49A.
    J Immunol. 1999 Nov 1;163(9):4931-8 PMID: 10528196
  40. Natural adjuvants: endogenous activators of dendritic cells.
    Nat Med. 1999 Nov;5(11):1249-55 PMID: 10545990
  41. Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells.
    J Immunol. 2000 Jan 1;164(1):9-12 PMID: 10604985
  42. Ox40-ligand has a critical costimulatory role in dendritic cell:T cell interactions.
    Immunity. 1999 Dec;11(6):689-98 PMID: 10626891
  43. Interaction of Ly-49D+ NK cells with H-2Dd target cells leads to Dap-12 phosphorylation and IFN-gamma secretion.
    J Immunol. 2000 Jan 15;164(2):603-11 PMID: 10623801
  44. Fc receptor signaling and trafficking: a connection for antigen processing.
    Immunol Rev. 1999 Dec;172:279-84 PMID: 10631953
  45. Impairment of antigen-presenting cell function in mice lacking expression of OX40 ligand.
    J Exp Med. 2000 Jan 17;191(2):365-74 PMID: 10637280
  46. Leukocyte migration: scent of the T zone.
    Curr Biol. 2000 Jan 13;10(1):R30-3 PMID: 10660291
  47. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells.
    J Exp Med. 2000 Feb 7;191(3):423-34 PMID: 10662788
  48. TRANCE, a tumor necrosis factor family member, enhances the longevity and adjuvant properties of dendritic cells in vivo.
    J Exp Med. 2000 Feb 7;191(3):495-502 PMID: 10662795
  49. Chemokines: a new classification system and their role in immunity.
    Immunity. 2000 Feb;12(2):121-7 PMID: 10714678
  50. Granulocyte-macrophage colony-stimulating factor delays neutrophil constitutive apoptosis through phosphoinositide 3-kinase and extracellular signal-regulated kinase pathways.
    J Immunol. 2000 Apr 15;164(8):4286-91 PMID: 10754327
  51. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes.
    J Immunol. 2000 May 15;164(10):4991-5 PMID: 10799849
  52. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
    Annu Rev Immunol. 2000;18:621-63 PMID: 10837071
  53. Innate immunity.
    N Engl J Med. 2000 Aug 3;343(5):338-44 PMID: 10922424
  54. The PI3 kinase, p38 SAP kinase, and NF-kappaB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte-derived dendritic cells.
    Blood. 2000 Aug 1;96(3):1039-46 PMID: 10910920
  55. Apoptotic pathways: paper wraps stone blunts scissors.
    Cell. 2000 Jul 7;102(1):1-4 PMID: 10929706
  56. Association of signal-regulatory proteins beta with KARAP/DAP-12.
    Eur J Immunol. 2000 Aug;30(8):2147-56 PMID: 10940905
  57. Toll-like receptors in the induction of the innate immune response.
    Nature. 2000 Aug 17;406(6797):782-7 PMID: 10963608
  58. DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming.
    Immunity. 2000 Sep;13(3):345-53 PMID: 11021532
  59. Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice.
    Immunity. 2000 Sep;13(3):355-64 PMID: 11021533
  60. The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta, ELC)-dependent mobilization of dendritic cells to lymph nodes.
    Cell. 2000 Nov 22;103(5):757-68 PMID: 11114332
  61. Series introduction: the transcription factor NF-kappaB and human disease.
    J Clin Invest. 2001 Jan;107(1):3-6 PMID: 11134170
  62. BH3-Only proteins-essential initiators of apoptotic cell death.
    Cell. 2000 Dec 8;103(6):839-42 PMID: 11136969
  63. Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family.
    Eur J Immunol. 2001 Mar;31(3):783-91 PMID: 11241283
  64. A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha, and contact sensitizers.
    J Immunol. 2001 Mar 15;166(6):3837-45 PMID: 11238627
  65. IgG Fc receptors.
    Annu Rev Immunol. 2001;19:275-90 PMID: 11244038
  66. Signal-regulatory protein alpha (SIRPalpha) but not SIRPbeta is involved in T-cell activation, binds to CD47 with high affinity, and is expressed on immature CD34(+)CD38(-) hematopoietic cells.
    Blood. 2001 May 1;97(9):2741-9 PMID: 11313266
  67. TREM-1 amplifies inflammation and is a crucial mediator of septic shock.
    Nature. 2001 Apr 26;410(6832):1103-7 PMID: 11323674
  68. TREM-1: a new regulator of innate immunity in sepsis syndrome.
    Nat Med. 2001 May;7(5):530-2 PMID: 11329047
  69. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells.
    Nucleic Acids Res. 1989 Aug 11;17(15):6419 PMID: 2771659
  70. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry.
    J Immunol Methods. 1991 Jun 3;139(2):271-9 PMID: 1710634
  71. Myeloma based expression system for production of large mammalian proteins.
    Trends Biotechnol. 1991 Apr;9(4):109-13 PMID: 1367388
  72. T cell-dependent induction of NF-kappa B in B cells.
    J Exp Med. 1993 Apr 1;177(4):1215-9 PMID: 8459216
  73. Regulation of the T-cell receptor delta enhancer by functional cooperation between c-Myb and core-binding factors.
    Mol Cell Biol. 1994 Jan;14(1):473-83 PMID: 8264615
  74. CD40L: a multi-functional ligand.
    Semin Immunol. 1993 Dec;5(6):401-12 PMID: 7510138
  75. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.
    J Exp Med. 1994 Apr 1;179(4):1109-18 PMID: 8145033
  76. Activation of NF-kappa B requires proteolysis of the inhibitor I kappa B-alpha: signal-induced phosphorylation of I kappa B-alpha alone does not release active NF-kappa B.
    Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):552-6 PMID: 7831327
  77. Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses.
    Cell. 1995 Jan 27;80(2):321-30 PMID: 7834752
  78. Two distinct regions of FC gamma RI initiate separate signalling pathways involved in endocytosis and phagocytosis.
    EMBO J. 1995 Feb 1;14(3):432-41 PMID: 7859733
  79. Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells.
    J Immunol. 1995 May 15;154(10):5071-9 PMID: 7730613
  80. Differential requirements for survival and proliferation of CD8 naïve or memory T cells.
    Science. 1997 Jun 27;276(5321):2057-62 PMID: 9197272
  81. Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells.
    Nature. 1997 Aug 21;388(6644):782-7 PMID: 9285591
  82. Expression and function of OX40 ligand on human dendritic cells.
    J Immunol. 1997 Oct 15;159(8):3838-48 PMID: 9378971
  83. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
    Nature. 1997 Nov 13;390(6656):175-9 PMID: 9367155
  84. 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB.
    Mol Cell Biol. 1998 Jan;18(1):558-65 PMID: 9418902
  85. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells.
    Nature. 1998 Feb 12;391(6668):703-7 PMID: 9490415
  86. Activation of OX40 signal transduction pathways leads to tumor necrosis factor receptor-associated factor (TRAF) 2- and TRAF5-mediated NF-kappaB activation.
    J Biol Chem. 1998 Mar 6;273(10):5808-14 PMID: 9488716
  87. Signaling through human killer cell activating receptors triggers tyrosine phosphorylation of an associated protein complex.
    Eur J Immunol. 1998 Feb;28(2):599-609 PMID: 9521070
  88. Dendritic cells and the control of immunity.
    Nature. 1998 Mar 19;392(6673):245-52 PMID: 9521319
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.194.8.1111
Published
2001-10-15
Pages
1111-22
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193511
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.194.8.1111 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2