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Dendritic Cell Precursors (dendritic + cell_precursor)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Identification of novel genes regulated by ,-melanocyte-stimulating hormone in murine bone marrow-derived dendritic cells

EXPERIMENTAL DERMATOLOGY, Issue 9 2004
T. Brzoska
Many strains of evidence indicate that ,-melanocyte-stimulating hormone (,-MSH) elicits its immunomodulatory activity via binding to melanocortin receptors (MC-Rs) expressed on monocytes and dendritic cells. In order to identify novel target genes regulated by ,-MSH in these cells, we prepared bone marrow-derived dendritic cell precursors from BALB/c mice and treated them with GM-CSF and IL-4 for 6 days. The MC-R profile on these immature dendritic cells was first determined by quantitative RT-PCR. Both transcripts for MC-1R and MC-5R were detected in these cells. Cells were subsequently stimulated with dinitrobenzene sulfonic acid (DNBS), ,-MSH or both substances for 2 or 16 h. After RNA preparation, cDNA synthesis and in vitro transcripton hybridization of biotinylated cRNA samples was performed on MG U74A Affymetrix gene chips. Data evaluation, cleansing, extraction and analysis of the more than 12 000 cloned genes and expressed sequence tags were performed using the GENE DATA ANALYST vs. 1 Expressionist software. Filter criteria included a minimum threshold of 100, normalization by the logarithmic mean and a quality setting of P < 0.04. Changes with a change factor of >2 were regarded as significant. As expected, stimulation with DNBS resulted in induction or upregulation of genes encoding proinflammatory cytokines, growth factors, signal transduction intermediates and transcription factors. Treatment with ,-MSH blocked the DNBS-driven upregulation of several known genes such as IL-1 or CD86. On the other hand, ,-MSH modulated the expression of several novel genes implicated in immunomodulation, e.g. IL-1, converting enzyme, IFN-, receptor, FK506-binding proteins or several neuropeptides and their receptors. These data indicate novel molecular targets by which ,-MSH exerts its immunomodulatory activities in immunocompetent cells. [source]

Granulocyte/macrophage-colony stimulating factor and interleukin-4 expand and activate type-1 dendritic cells (DC1) when administered in vivo to cancer patients

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2003
Sylvia 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]

Characterization of human peritoneal dendritic cell precursors and their involvement in peritonitis

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005
M. L. McCully
Summary Scattered evidence suggests that the human peritoneal cavity contains cells of the dendritic cell (DC) lineage but their characterization is missing. Here, we report that the peritoneal cavity of normal subjects and of stable patients on peritoneal dialysis (PD) contains a population of CD14+ cells that can differentiate into DCs or macrophages. Within this pool, we characterized a CD14+CD4+ cell subset (2·2% of the peritoneal cells) fulfilling the definition of myeloid DC precursors or pre-DC1 cells. These cells expressed high levels of HLA-DR, CD13, CD33, and CD86, and low levels of CD40, CD80, CD83, CD123, CD209, TLR-2 and TLR-4. These cells retained CD14 expression until late stages of differentiation, despite concomitant up-regulation of DC-SIGN (CD209), CD1a, CD80 and CD40. Peritoneal pre-DC1 cells had endocytic capacity that was down-regulated upon LPS/IFN-, stimulation, were more potent allo-stimulators than peritoneal CD14+CD4,/lo cells and monocyte-derived macrophages, and induced Th1 cytokine responses. More importantly, the number of peritoneal pre-DC1 cells increased during PD-associated peritonitis, with a different profile for Gram positive and Gram negative peritonitis, suggesting that these cells participate in the induction of peritoneal adaptive immune responses, and may be responsible for the bias towards Th1 responses during peritonitis. [source]

T cell inflammatory response, Foxp3 and TNFRS18-L regulation of peripheral blood mononuclear cells from patients with nasal polyps-asthma after staphylococcal superantigen stimulation

CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2010
C. A. Pérez Novo
Cite this as: C. A. Pérez Novo, M. Jedrzejczak-Czechowicz, A. Lewandowska-Polak, C. Claeys, G. Holtappels, P. Van Cauwenberge, M. L. Kowalski and C. Bachert, Clinical & Experimental Allergy, 2010 (40) 1323,1332. Summary Background Staphylococcal superantigens may modulate airway inflammatory disease. Objective We assessed the effect of Staphylococcus aureus enterotoxin B (SEB) on T cell activation in patients with nasal polyps and asthma, and its possible link to aspirin hypersensitivity. Methods Leucocytes were isolated from five healthy subjects (controls), five asthmatics with nasal polyps without (NP-ATA) and five with aspirin-induced asthma (NP-AIA). Cells were incubated with increasing concentrations of SEB for 4 and 18 h. Release of TH1/TH2 cytokines was assessed by Cytometric Bead-Array. Foxp3 and TNFRS18-L expression were analysed by qPCR and flow cytometry. Results After 4 and 18 h, SEB significantly increased IFN-gamma, IL-4, TNF-alpha, IL-5 and IL-2 concentrations in supernatants of both NP polyp groups compared with controls. Baseline Foxp3 was significantly decreased in both NP-asthma groups. Incubation with SEB for 4 h induced a limited up-regulation of Foxp3 in NP-AIA patients, which was switched off consecutively. Foxp3 was significantly up-regulated in the control group after 18 h, but not in the NP-asthmatic groups. In parallel, TNFRS18-L mRNA significantly increased after 18 h in the NP-asthma groups compared with control subjects. This molecule was highly expressed in CD11c+CD14+ cells and its levels increased after 18 and 24 h culture in the NP-asthma patients. Conclusion SEB induces both TH1 and TH2 pro-inflammatory responses in patients with nasal polyps and asthma regardless of the presence of aspirin hypersensitivity. The nature of this response may be linked to a basal deficiency of Foxp3 observed in the NP-asthmatic patients and/or to the up-regulation of TNFRS18-L on monocytes/dendritic cell precursors. [source]