Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

TCDD induced gene expression changes in dendritic cells

ABSTRACT: Effect of the over activation of the aryl hydrocarbon receptor on gene expression of spleen derived dendritic cells. 8-12 week old, female C57BL6 mice were injected 10 Âµg/kg TCDD i.p. or solvent control. After 24 h mice were sacrificed and splenic dendritic cells purified by MACS sorting.

ORGANISM(S): Mus musculus

SUBMITTER: Markus Frericks

PROVIDER: E-GEOD-13719 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.

Frericks Markus M Temchura Vladimir V VV Majora Marc M Stutte Susanne S Esser Charlotte C

Biological chemistry 20060901 9

The ligand-activated aryl hydrocarbon receptor (AHR) is known to modulate many genes in a highly cell-specific manner, either directly or indirectly via secondary effects. In contrast, little is known about the effects of AHR deficiency on gene expression balance. We compared the transcriptome of CD4 T cells from AHR-/- mice and wild-type mice; 390 genes, many of them immunotypic, were deregulated in AHR-deficient CD4 cells. TCDD-induced transcriptome changes correlated with the AHR expression l ...[more]

PMID: 16972790

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Project description:The physiological function of the immune system and the response to therapeutic immunomodulators may be sensitive to combinatorial cytokine micro-environments that shape the responses of specific immune cells. Previous work shows that paracrine cytokines released by virus-infected human dendritic cells (DC) can dictate the maturation state of naM-CM-/ve DCs. To understand the effects of paracrine signaling, we systematically studied the effects of combinations cytokines in this complex mixture in generating an antiviral state. After naM-CM-/ve DCs were exposed to either IFNM-NM-2 or to paracrine signaling released by DCs infected by Newcastle Disease Virus (NDV), microarray analysis revealed a large number of genes that were differently regulated by the DC-secreted paracrine signaling. In order to identify the cytokine mechanisms involved, we identified 20 cytokines secreted by NDV infected DCs for which the corresponding receptor gene is expressed in naM-CM-/ve DCs. By exposing cells to all combinations of 19 cytokines (leave-one-out studies) we identified 5 cytokines (IFNM-NM-2, TNFM-NM-1, IL-1M-oM-^AM-", TNFSF15 and IL28) as candidates for regulating DC maturation markers. Subsequent experiments identified IFNM-NM-2, TNFM-NM-1 and IL1M-oM-^AM-" as the major synergistic contributors to this antiviral state. This finding was supported by infection studies in vitro, by T cell activation studies and by in vivo infection studies in mouse. Combination of cytokines can cause response states in DCs that differ from those achieved by the individual cytokines alone. These results suggest that the cytokine microenvironment may act via a combinatorial code to direct the response state of specific immune cells. Further elucidation of this code may provide insight into responses to infection and neoplasia as well as guide the development of combinatorial cytokine immunomodulation for infectious, autoimmune and immunosurveillance-related diseases. Cells exposed to the supernatant of NDV infected cells were compared to NDV infected cells, IFNM-NM-2 treated cells and naM-CM-/ve dendritic cells after 8 hours.

Dataset Information

TCDD induced gene expression changes in dendritic cells

Publications

Transcriptional signatures of immune cells in aryl hydrocarbon receptor (AHR)-proficient and AHR-deficient mice.

Similar Datasets

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