Genomics

Dataset Information

296

The Cytokines IL-21 and GM-CSF have Opposing Regulatory Roles in the Apoptosis of Conventional Dendritic Cells


ABSTRACT: 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. 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

ORGANISM(S): Mus musculus  

SUBMITTER: Brian L Kelsall   Warren J Leonard  Peng Li  Lu Wang  Chi-Keung Wan  Rosanne Spolski  Elizabeth A Wong  Jangsuk Oh  Zu-Xi Yu 

PROVIDER: E-GEOD-27161 | ArrayExpress | 2013-02-14

SECONDARY ACCESSION(S): SRP005649GSE27161PRJNA137403

REPOSITORIES: GEO, ArrayExpress, ENA

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