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Monocyte-derived DC (monocyte-derived + dc)
Selected AbstractsViral infection and Toll-like receptor agonists induce a differential expression of type,I and , interferons in human plasmacytoid and monocyte-derived dendritic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2004Eliana Abstract In humans, the type,I interferon (IFN) family consists of 13 IFN-, subtypes, IFN-, and IFN-o the newly discovered IFN-like family consists of IFN-,1, -,2 and -,3. We have investigated the expression of type,I and , IFN genes following virus infections or Toll-like receptor (TLR) triggering in monocyte-derived DC (MDDC) and plasmacytoid DC (pDC). We found thatall IFN-,, -,, -o and -, subtypes are expressed in influenza-virus-infected MDDC or pDC. Conversely, differential type,I IFN gene transcription was induced in MDDC and pDC stimulated by specific TLR agonists. TLR-9 stimulation by CpG DNA induced the expression of all IFN-,, -,, -o and -, subtypes in pDC, whereas TLR-4 stimulation by LPS, or TLR-3 stimulation bypoly I:C, induced only IFN-, and IFN-, gene expression in MDDC. The expression pattern of IFN regulatory factor (IRF)-5 and IRF-7 in MDDC and pDC was also determined. IRF-5 was constitutively expressed in the two DC subsets whereas IRF-7 was constitutive in pDC but its expression was induced along MDDC maturation. Overall, our data indicate that the coordinated expression of IFN-, with IFN-, would be of crucial importance for the maturation of DC. [source] Corticotropin-releasing factor decreases IL-18 in the monocyte-derived dendritic cellEXPERIMENTAL DERMATOLOGY, Issue 3 2009Hee Jung Lee Abstract:, Recent evidence suggests that crosstalk between mast cells, nerves and keratinocytes might be involved in the exacerbation of inflammatory conditions by stress, but the mechanism by which this occurs remains unclear. Corticotropin-releasing factor (CRF), which activates the hypothalamo-pituitary-adrenal (HPA) axis under stress, also has pro-inflammatory peripheral effects. However, there have been no reports about CRF receptor expression and the functional role of CRF in the dendritic cell (DC), which is considered to be the link between allergen uptake and the clinical manifestations of allergic diseases, such as atopic dermatitis. The purpose of this study was to investigate the expression of CRF receptors and the functional role of CRF in the monocyte-derived DC (MoDC) of atopic dermatitis patients and non-atopic healthy controls. In this study, mRNAs for CRF-R1, and 1,, as well as the CRF-R1 protein, were detected in MoDCs. CRF-R2, (but not R2, or R2,) mRNA and the CRF-R2 protein were present in MoDCs. Exposure of DCs to CRF resulted in a decrease of IL-18 in both atopic dermatitis patients and non-atopic healthy controls. However, CRF did not alter the expression of IL-6, CCL17, CCL18, and CCL22. Therefore, our results demonstrate that CRF could modulate immune responses by acting directly upon DCs. [source] Histamine and prostaglandin E2 up-regulate the production of Th2-attracting chemokines (CCL17 and CCL22) and down-regulate IFN-,-induced CXCL10 production by immature human dendritic cellsIMMUNOLOGY, Issue 4 2006Anne McIlroy Summary Effector memory T helper 2 (Th2) cells that accumulate in target organs (i.e. skin or bronchial mucosa) have a central role in the pathogenesis of allergic disorders. To date, the factors that selectively trigger local production of Th2-attracting chemokines remain poorly understood. In mucosa, at the sites of allergen entry, immature dendritic cells (DC) are in close contact with mast cells. Histamine and prostaglandin E2 (PGE2) are two mediators released by allergen-activated mast cells that favour the polarization of maturing DC into Th2-polarizing cells. We analysed here the effects of histamine and PGE2 on the prototypic, Th2-(CCL17, CCL22) versus Th1-(CXCL10) chemokine production by human DC. We report that histamine and PGE2 dose-dependently up-regulate CCL17 and CCL22 by monocyte-derived immature DC. These effects were potentiated by tumour necrosis factor-,, still observed in the presence of the Th1-cytokine interferon-, (IFN-,) and abolished by the immunomodulatory cytokine interleukin-10. In addition, histamine and PGE2 down-regulated IFN-,-induced CXCL10 production by monocyte-derived DC. These properties of histamine and PGE2 were observed at the transcriptional level and were mediated mainly through H2 receptors for histamine and through EP2 and EP4 receptors for PGE2. Finally, histamine and PGE2 also up-regulated CCL17 and CCL22 and decreased IFN-,-induced CXCL10 production by purified human myeloid DC. In conclusion, these data show that, in addition to polarizing DC into mature cells that promote naļve T-cell differentiation into Th2 cells, histamine and PGE2 may act on immature DC to trigger local Th2 cell recruitment through a selective control of Th1/Th2-attracting chemokine production, thereby contributing to maintain a microenvironment favourable to persistent immunoglobulin E synthesis. [source] Granulocyte/macrophage-colony stimulating factor and interleukin-4 expand and activate type-1 dendritic cells (DC1) when administered in vivo to cancer patientsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2003Sylvia M. Kiertscher Abstract Two rare populations of cells with the features of dendritic cell precursors (preDC) can be identified in human peripheral blood. PreDC1 are HLA-DR+/CD11c+ cells which mature into DC1 capable of stimulating Th1 responses. In contrast, preDC2 are HLA-DR+/CD11c,/CD123+ cells that promote Th2 responses when matured into DC2. We hypothesized that administration of GM-CSF and IL-4, growth factors for DC1, would specifically augment the number and function of circulating DC1 in vivo. Patients with advanced metastatic cancer were treated with GM-CSF (2.5 ,g/kg/day) and IL-4 (4 or 6 ,g/kg/day) for 7 days. Cytokine administration at the highest IL-4 dose produced an average 2.3-fold increase in preDC2 number, but a 6.5-fold increase in preDC1, resulting in an increased ratio of circulating preDC1:preDC2 from 1.4:1 pre-treatment to 4.3:1 after cytokine therapy. DC1 precursors identified after in vivo therapy were larger, more complex and expressed higher levels of HLA-DR, CD11c and CD80 than pre-treatment cells. DC1 isolated from the peripheral blood of patients receiving GM-CSF/IL-4 therapy demonstrated MLR activity comparable to that of monocyte-derived DC generated in vitro from the patients' pre-treatment blood using GM-CSF and IL-4. We conclude that systemic administration of GM-CSF and IL-4 preferentially expands and matures the preDC1 population in vivo. These effects correlate with antigen-presenting activity, providing a mechanism by which systemic GM-CSF and IL-4 might stimulate anti-tumor immunity in vivo. © 2003 Wiley-Liss, Inc. [source] Monocyte-derived dendritic cells from HCV-infected patients transduced with an adenovirus expressing NS3 are functional when stimulated with the TLR3 ligand poly(I:C)JOURNAL OF VIRAL HEPATITIS, Issue 11 2008I. Echeverrķa Summary., Dendritic cells (DC) transfected with an adenovirus encoding hepatitis C virus (HCV) NS3 protein (AdNS3) induce potent antiviral immune responses when used to immunize mice. However, in HCV infected patients, controversial results have been reported regarding the functional properties of monocyte-derived DC (MoDC), a cell population commonly used in DC vaccination protocols. Thus, with the aim of future vaccination studies we decided to characterize MoDC from HCV patients transfected with AdNS3 and stimulated with the TLR3 ligand poly(I:C). Phenotypic and functional properties of these cells were compared with those from MoDC obtained from uninfected individuals. PCR analysis showed that HCV RNA was negative in MoDC from patients after the culture period. Also, phenotypic analysis of these cells showed lower expression of CD80, CD86, and CD40, but similar expression of HLA-DR molecules as compared to MoDC from uninfected individuals. Functional assays of MoDC obtained from patients and controls showed a similar ability to activate allogeneic lymphocytes or to produce IL-12 and IL-10, although lower IFN-, levels were produced by cells from HCV patients after poly(I:C) stimulation. Moreover, both groups of MoDC induced similar profiles of IFN-, and IL-5 after stimulation of allogeneic T-cells. Finally, migration assays did not reveal any difference in their ability to respond to CCL21 chemokine. In conclusion, MoDC from HCV patients are functional after transduction with AdNS3 and stimulation with poly(I:C). These findings suggest that these cells may be useful for therapeutic vaccination in chronic HCV infection. [source] CD1a expression defines an interleukin-12 producing population of human dendritic cellsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009M. Cernadas Summary Human and murine dendritic cell (DC) subsets are often defined by phenotypic features that predict their functional characteristics. In humans and mice, DC have been shown to have the ability to polarize naive CD4 T cells to a T helper type 1 (Th1) or Th2 phenotype. However, human myeloid DC generated from monocytes (monocyte-derived DC) have often been regarded as a homogeneous population, both phenotypically and functionally. Monocytes give rise to subpopulations of DC in vitro that can be separated on the basis of their expression of CD1a, a well-described DC subset marker. Importantly, we show that the CD1a+ DC subset produces significant quantities of interleukin-12p70 (IL-12p70) upon stimulation and, similar to the murine CD8,+ DC subset, can polarize naive CD4+ T cells to a Th1 phenotype. In contrast, CD1a, DC, similar to murine CD8,, DC, do not produce significant amounts of IL-12p70 upon stimulation or polarize T cells to a Th1 phenotype. Like monocyte-derived DC, CD1a+ and CD1a, DC subsets obtained from CD34+ haematopoietic progenitors under distinct culture conditions were found to have these same features, suggesting that CD1a expression is a marker for myeloid DC that are a major source of IL-12 and Th1 CD4+ T cell polarization in man. [source] | ||||||||||