|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Feb 14, 2013 |
Title |
The Cytokines IL-21 and GM-CSF have Opposing Regulatory Roles in the Apoptosis of Conventional Dendritic Cells |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
Summary |
Interleukin-21 (IL-21) has broad actions on T- and B-cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive α-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive-transfer of wild-type CD4+ T cells caused more severe colitis with increased DCs and interferon (IFN)-γ-producing CD4+ T cells in Il21r-/-Rag2-/- mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2-/- mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response.
|
|
|
Overall design |
Total 6 samples were examined. Splenic dendritic cells were treated with IL-21 and/or GM-CSF studying STAT3 and STAT5B binding in the genome
|
|
|
Contributor(s) |
Wan C, Oh J, Li P, Wong EA, Spolski R, Wang L, Yu Z, Kelsall BL, Leonard WJ |
Citation(s) |
23453633 |
|
Submission date |
Feb 08, 2011 |
Last update date |
May 15, 2019 |
Contact name |
Peng Li |
E-mail(s) |
peng.li@nih.gov
|
Organization name |
NIH
|
Department |
NHLBI
|
Lab |
LMI
|
Street address |
9000 Rockville Pike
|
City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
|
|
Platforms (1) |
GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
|
Samples (6)
|
|
Relations |
SRA |
SRP005649 |
BioProject |
PRJNA137403 |
Supplementary file |
Size |
Download |
File type/resource |
GSE27161_RAW.tar |
597.7 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
|
|
|
|
|