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Series GSE43456 Query DataSets for GSE43456
Status Public on Sep 19, 2013
Title Cytokine-dependent dendritic cell differentiation in the splenic microenvironment
Organism Mus musculus
Experiment type Expression profiling by array
Summary The dendritic cell (DC)-derived chemokine CCL17, a ligand of CCR4, has been shown to promote various inflammatory diseases such as atopic dermatitis, atherosclerosis, and inflammatory bowel disease. Under steady state conditions, and even after systemic stimulation with lipopolysaccharide, CCL17 is not expressed in resident splenic DC as opposed to CD8-CD11b+ lymph node (LN) DC, which produce large amounts of CCL17, in particular after maturation. Upon systemic NKT cell activation through alpha-galactosylceramide stimulation, however, CCL17 can be upregulated in both CD8- and CD8+ splenic DC subsets and enhances cross-presentation of exogenous antigens. Based on genome wide expression profiling, we now show that splenic DC are susceptible to Interferon-gamma (IFNgamma) mediated suppression of CCL17, whereas LN DC are much less responsive to IFNgamma and downregulate the IFNgamma receptor. Under inflammatory conditions, particularly in the absence of IFNgamma signaling in IFNgamma receptor deficient mice, CCL17 expression is strongly induced in a major proportion of splenic DC by the action of granulocyte-macrophage colony stimulating factor (GM-CSF) in concert with interleukin (IL)-4. Our findings demonstrate that the local cytokine milieu and differential cytokine responsiveness of DC subsets regulate lymphoid organ specific immune responses at the level of chemokine expression.
 
Overall design 15 h after pretreatment with 100 µg LPS, spleens and LN (MLN and PLN) from CCL17E/+ mice were harvested and DC-enriched cell suspensions of the respective organs were stained for NK1.1, CD8alpha, CD11c and CD11b. For isolation of LN DC, NK1.1-CD8alpha-CD11c+CD11b+ cells expressing CCL17/EGFP were sorted (FACSAria). Splenic DC were sorted in parallel from the same mice, but only CCL17/EGFP-negative cells expressing the same markers were selected. After the sort, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.
 
Contributor(s) Globisch T, Lukacs-Kornek V, Degrandi D, Dresing P, Alferink J, Lang R, Pfeffer K, Beyer M, Weighardt H, Kurts C, Ulas T, Schultze JL, Förster I
Citation(s) 24136200
Submission date Jan 11, 2013
Last update date Jan 16, 2019
Contact name Joachim Schultze
E-mail(s) j.schultze@uni-bonn.de
Organization name LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
Department Genomics and Immunoregulation
Street address Carl-Troll-Strasse 31
City Bonn
State/province NRW
ZIP/Postal code 53115
Country Germany
 
Platforms (1)
GPL6887 Illumina MouseWG-6 v2.0 expression beadchip
Samples (8)
GSM1062732 CCL17 positve rep1
GSM1062733 CCL17 negative rep1
GSM1062734 CCL17 negative rep2
Relations
BioProject PRJNA186443

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43456_RAW.tar 15.8 Mb (http)(custom) TAR
GSE43456_non_normalized.txt.gz 2.7 Mb (ftp)(http) TXT
Processed data included within Sample table

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