Interleukin 10 Induces the Maturation of Putative Tolerogenic Monocyte-derived Dendritic Cells as Revealed by GeneArray Analysis

IL-10 is a multifunctional cytokine with known inhibitory effect on DC maturation. In the present study, we show that the presence of IL-10 during the first 6 days of maturation of Mo-DC has severe effects on the phenotype with IL-10 treated Mo-DC retaining a high expression of factors involved in antigen uptake and having low expression of costimulatory factors and MHC II. The effect of IL-10 on DC maturation is further characterized by a comprehensive investigation of the expression profile of 12500 genes using GeneArrays and comparing the data for IL-10 treated and untreated Mo-DC at day 6 and 8 with monocytes and macrophages. The data is confirmed with semi-quantitative RT-PCR. We find that the transcriptional pattern of IL-10 treated Mo-DC at day 6 and day 8 is distinct from both untreated Mo-DC and macrophages. IL-10 induces the expression of genes coding for CCL18, ILT3, ILT4 and TGFβ while inhibiting the expression of IL-12 p40 mRNA, and genes coding for CCL17, CCL19 and CCL22 suggesting a likely effect of IL-10 on Mo-DC maturation to be the generation of tolerogenic Mo-DC.

[1]  S. Husby,et al.  Alternative splice variants of the human PD-1 gene. , 2005, Cellular immunology.

[2]  S. Lillevang,et al.  Serum Concentration of the Growth Medium Markedly Affects Monocyte‐Derived Dendritic Cells' Phenotype, Cytokine Production Profile and Capacities to Stimulate in MLR , 2004, Scandinavian journal of immunology.

[3]  Yoshiro Kobayashi,et al.  Immature dendritic cells reduce proinflammatory cytokine production by a coculture of macrophages and apoptotic cells in a cell‐to‐cell contact‐dependent manner , 2004, Journal of leukocyte biology.

[4]  Ruth Croxton,et al.  IL-10-Conditioned Dendritic Cells, Decommissioned for Recruitment of Adaptive Immunity, Elicit Innate Inflammatory Gene Products in Response to Danger Signals1 , 2004, The Journal of Immunology.

[5]  Francesco M Marincola,et al.  Cytokine and chemokine expression profiles of maturing dendritic cells using multiprotein platform arrays. , 2004, Cytokine.

[6]  D. Mancini,et al.  High expression of ILT3 and ILT4 is a general feature of tolerogenic dendritic cells. , 2003, Transplant immunology.

[7]  A. Aderem,et al.  The Toll-Like Receptor 5 Stimulus Bacterial Flagellin Induces Maturation and Chemokine Production in Human Dendritic Cells1 , 2003, The Journal of Immunology.

[8]  M. Felaco,et al.  IL-10, an inflammatory/inhibitory cytokine, but not always. , 2003, Immunology letters.

[9]  A. Mantovani,et al.  Unique Regulation of CCL18 Production by Maturing Dendritic Cells1 , 2003, The Journal of Immunology.

[10]  A. Enk,et al.  Interleukin-10-treated dendritic cells modulate immune responses of naive and sensitized T cells in vivo. , 2002, The Journal of investigative dermatology.

[11]  S A Bustin,et al.  Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems. , 2002, Journal of molecular endocrinology.

[12]  M. Colonna,et al.  Tolerization of dendritic cells by TS cells: the crucial role of inhibitory receptors ILT3 and ILT4 , 2002, Nature Immunology.

[13]  G. Aversa,et al.  IL-10 alters DC function via modulation of cell surface molecules resulting in impaired T-cell responses. , 2002, Cellular immunology.

[14]  Meng-tse Wu,et al.  Cutting Edge: CCR4 Mediates Antigen-Primed T Cell Binding to Activated Dendritic Cells , 2001, The Journal of Immunology.

[15]  K. Matsushima,et al.  Mammalian and Viral IL-10 Enhance C-C Chemokine Receptor 5 but Down-Regulate C-C Chemokine Receptor 7 Expression by Myeloid Dendritic Cells: Impact on Chemotactic Responses and In Vivo Homing Ability1 , 2001, The Journal of Immunology.

[16]  P. Allavena,et al.  Dendritic cells as a major source of macrophage‐derived chemokine/CCL22 in vitro and in vivo , 2001, European journal of immunology.

[17]  L. Kanz,et al.  Tumor necrosis factor alpha and CD40 ligand antagonize the inhibitory effects of interleukin 10 on T-cell stimulatory capacity of dendritic cells. , 2000, Cancer research.

[18]  B. Ludviksson,et al.  The effect of TGF‐β1 on immune responses of naïve versus memory CD4+ Th1/Th2 T cells , 2000, European journal of immunology.

[19]  A. Zlotnik,et al.  Chemokines: a new classification system and their role in immunity. , 2000, Immunity.

[20]  K. Matsushima,et al.  Serial analysis of gene expression in human monocytes and macrophages. , 1999, Blood.

[21]  C. Mackay,et al.  Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses. , 1998, Immunology today.

[22]  S. Goerdt,et al.  Alternative macrophage activation-associated CC-chemokine-1, a novel structural homologue of macrophage inflammatory protein-1 alpha with a Th2-associated expression pattern. , 1998, Journal of immunology.

[23]  P. Allavena,et al.  IL‐10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages , 1998, European journal of immunology.

[24]  A. Enk,et al.  Induction of tolerance by IL-10-treated dendritic cells. , 1997, Journal of immunology.

[25]  M. Moser,et al.  Effect of interleukin‐10 on dendritic cell maturation and function , 1997, European journal of immunology.

[26]  F. Marincola,et al.  The dual role of IL-10. , 2003, Trends in immunology.

[27]  R. Coffman,et al.  Interleukin-10 and the interleukin-10 receptor. , 2001, Annual review of immunology.