Maturation of human monocyte-derived dendritic cells studied by microarray hybridization.

We compared the transcript profiles of human myeloid immature dendritic (IDC) cells and mature dendritic cells (MDC) by hybridization of cell-derived cDNA to DNA probes immobilized on microarrays. The microarrays contained probes for 4110 known genes. We report maturation-dependent changes in transcription of clusters of differentiation, cytokines, cytokine receptors, chemokines, chemokine receptors, neuropeptides, adhesion molecules, and other genes. We identified 1124 transcripts expressed in IDC and 1556 transcripts expressed in MDC. Maturation increased the levels of 291 transcripts twofold or more and reduced the levels of 78 transcripts to one-half or less than in IDC. We identified a concerted maturation-stage-dependent transcription of the variable chains of the members of the gamma-chain-cytokine receptor family IL-4R, IL-7R, and IL-15R. Also, we found the reversal of the ratio of transcripts for galectin-3 and galectin-9 upon maturation. We identified maturation-dependent changes in the levels of transcripts for numerous genes encoding proteins previously undetected in dendritic cells such as indoleamine 2,3-deoxygenase, Epstein-Barr virus induced protein 3 and kinesin-2. Moreover, MDC transcribed and translated insulin like growth factor-1 receptor, transforming growth factor alpha, and neuropeptide Y.

[1]  Gregory S. Schultz,et al.  EGF and TGF‐α in wound healing and repair , 1991 .

[2]  R. Zuberi,et al.  Epsilon BP, a beta-galactoside-binding animal lectin, recognizes IgE receptor (Fc epsilon RI) and activates mast cells. , 1993, Biochemistry.

[3]  K. Kinzler,et al.  Serial Analysis of Gene Expression , 1995, Science.

[4]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[5]  Liangji Zhou,et al.  Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. , 1995, Journal of immunology.

[6]  L. Baum,et al.  Apoptosis of T cells mediated by galectin-1 , 1995, Nature.

[7]  C Danieli,et al.  Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products , 1995, The Journal of experimental medicine.

[8]  P. Brown,et al.  A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. , 1996, Genome research.

[9]  O. Yoshie,et al.  Molecular Cloning of a Novel T Cell-directed CC Chemokine Expressed in Thymus by Signal Sequence Trap Using Epstein-Barr Virus Vector* , 1996, The Journal of Biological Chemistry.

[10]  D. Carbone,et al.  Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells , 1996, Nature Medicine.

[11]  W. Greene,et al.  Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the beta-galactoside-binding lectin, galectin-3. , 1996, American Journal of Pathology.

[12]  E. Kieff,et al.  A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes , 1996, Journal of virology.

[13]  D. Hart,et al.  Dendritic cells: unique leukocyte populations which control the primary immune response. , 1997, Blood.

[14]  H. Klocker,et al.  Prostaglandin E2 and Tumor Necrosis Factor ␣ Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production , 1997 .

[15]  A. Enk,et al.  Induction of IL-15 messenger RNA and protein in human blood-derived dendritic cells: a role for IL-15 in attraction of T cells. , 1997, Journal of immunology.

[16]  A. Kumar,et al.  Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin. , 1997, The Journal of clinical investigation.

[17]  A. Enk,et al.  Pro‐inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum‐free conditions , 1997, European journal of immunology.

[18]  L. Baum,et al.  Galectin-1, an Endogenous Lectin Produced by Thymic Epithelial Cells, Induces Apoptosis of Human Thymocytes , 1997, The Journal of experimental medicine.

[19]  V. Verhasselt,et al.  Interleukin‐10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin‐4 and granulocyte/ macrophage‐colony‐stimulating factor , 1997, European journal of immunology.

[20]  A. Meyerhans,et al.  Monocyte-derived dendritic cells represent a transient stage of differentiation in the myeloid lineage. , 1997, Immunobiology.

[21]  G. Boltz‐Nitulescu,et al.  Galectin-3 inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven rat bone marrow cell proliferation and GM-CSF-induced gene transcription. , 1997, Immunobiology.

[22]  J. Galon,et al.  Soluble CD16/Fc gamma RIII induces maturation of dendritic cells and production of several cytokines including IL-12. , 1997, Advances in experimental medicine and biology.

[23]  P. Allavena,et al.  Human Macrophage–derived Chemokine (mdc), a Novel Chemoattractant for Monocytes, Monocyte-derived Dendritic Cells, and Natural Killer Cells , 1997 .

[24]  J. Sodroski,et al.  CCR5 has an expanded ligand-binding repertoire and is the primary receptor used by MCP-2 on activated T cells. , 1998, Cellular immunology.

[25]  H. Inohara,et al.  Galectin-3 stimulates cell proliferation. , 1998, Experimental cell research.

[26]  R. Mebius,et al.  Lymphocyte triggering via L‐selectin leads to enhanced galectin‐3‐mediated binding to dendritic cells , 1998, European journal of immunology.

[27]  B. Hock,et al.  Human dendritic cells express functional interleukin-7. , 1998, Immunobiology.

[28]  L. Kanz,et al.  Generation of Functional Human Dendritic Cells From Adherent Peripheral Blood Monocytes by CD40 Ligation in the Absence of Granulocyte-Macrophage Colony-Stimulating Factor , 1998 .

[29]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[30]  P. Kalinski,et al.  Glucocorticoids inhibit bioactive IL-12p70 production by in vitro-generated human dendritic cells without affecting their T cell stimulatory potential. , 1998, Journal of immunology.

[31]  U. Grohmann,et al.  IL-12 acts directly on DC to promote nuclear localization of NF-kappaB and primes DC for IL-12 production. , 1998, Immunity.

[32]  J. Austyn,et al.  Dendritic cell chemotaxis and transendothelial migration are induced by distinct chemokines and are regulated on maturation , 1998, European journal of immunology.

[33]  Y. Yamaguchi,et al.  EBI1/CCR7 is a new member of dendritic cell chemokine receptor that is up-regulated upon maturation. , 1998, Journal of immunology.

[34]  V. Castronovo,et al.  Transglutaminase-mediated oligomerization of galectin-3 modulates human melanoma cell interactions with laminin. , 1998, Cell adhesion and communication.

[35]  D. Munn,et al.  Prevention of allogeneic fetal rejection by tryptophan catabolism. , 1998, Science.

[36]  J. Renauld,et al.  Signalling by cytokines interacting with the interleukin-2 receptor gamma chain. , 1998, Cytokines, cellular & molecular therapy.

[37]  J C Gluckman,et al.  Dendritic cells as the terminal stage of monocyte differentiation. , 1998, Journal of immunology.

[38]  M. Rihanek,et al.  STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13. , 1998, Journal of immunology.

[39]  A. D. Amo,et al.  Galectin-3 down-regulates IL-5 gene expression on different cell types. , 1998, Journal of immunology.

[40]  R. Kooijman,et al.  The role of growth hormone and insulin-like growth factors in the immune system , 1998, Cellular and Molecular Life Sciences CMLS.

[41]  R Bonecchi,et al.  Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties. , 1998, Journal of immunology.

[42]  C. Caux,et al.  Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites , 1998, The Journal of experimental medicine.

[43]  B. Gebhardt,et al.  The inherent quantitative capacity of the reverse transcription-polymerase chain reaction. , 1999, Analytical biochemistry.

[44]  D. Munn,et al.  Inhibition of  T Cell Proliferation by Macrophage Tryptophan Catabolism , 1999, The Journal of experimental medicine.

[45]  K. Matsushima,et al.  Serial analysis of gene expression in human monocyte-derived dendritic cells. , 1999, Blood.

[46]  T. Honjo,et al.  Fractalkine and macrophage‐derived chemokine: T cell‐attracting chemokines expressed in T cell area dendritic cells , 1999, European journal of immunology.

[47]  L. A. Lewis,et al.  Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis but inhibit IL-2 production and proliferation. , 1999, Journal of immunology.

[48]  D. Botstein,et al.  The transcriptional program in the response of human fibroblasts to serum. , 1999, Science.

[49]  Antonio Lanzavecchia,et al.  Distinct patterns and kinetics of chemokine production regulate dendritic cell function , 1999, European journal of immunology.

[50]  A. Melcher,et al.  Heat shock protein 70 induced during tumor cell killing induces Th1 cytokines and targets immature dendritic cell precursors to enhance antigen uptake. , 1999, Journal of immunology.

[51]  H. Saeki,et al.  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. , 1999, Journal of immunology.

[52]  A. Dietz,et al.  Dexamethasone inhibits dendritic cell maturation by redirecting differentiation of a subset of cells , 1999, Journal of leukocyte biology.

[53]  D. Munn,et al.  Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? , 1999, Immunology today.

[54]  T. Ito,et al.  A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells. , 1999, Journal of immunology.

[55]  Hanno Langen,et al.  Maturation, Activation, and Protection of Dendritic Cells Induced by Double-stranded RNA , 1999, The Journal of experimental medicine.

[56]  L. Flechner,et al.  Insulin-Like Growth Factor I Synergizes with Interleukin 4 for Hematopoietic Cell Proliferation Independent of Insulin Receptor Substrate Expression , 1999, Molecular and Cellular Biology.

[57]  P. Bulur,et al.  Optimizing preparation of normal dendritic cells and bcr-abl+ mature dendritic cells derived from immunomagnetically purified CD14+ cells. , 2000, Journal of hematotherapy & stem cell research.