Granulocyte‐macrophage colony‐stimulating factor induces a unique set of STAT factors in murine dendritic cells

Welte, Thomas; Koch, Franz; Schuler, Gerold; Lechner, Judith; Doppler, Wolfgang; Heufler, Christine

doi:10.1002/eji.1830271038

Cited by 42 publications

(27 citation statements)

References 32 publications

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“…Activated STAT5 may bind IFN-␥-activated sequence (GAS) elements found in CIITA PIII. In addition, there are reports in some cell types that GM-CSF can activate STAT1, which also could bind GAS elements (43,44). Our preliminary results suggest that in addition to STAT5, STAT1 may be phosphorylated following GM-CSF treatment (T. M. C. Hornell, unpublished data).…”

Section: Discussionsupporting

confidence: 55%

Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

Hornell

Beresford

Bushey

et al. 2003

The Journal of Immunology

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GM-CSF stimulates the growth and differentiation of hematopoietic progenitors and also affects mature cell function. These effects have led to the use of GM-CSF as a vaccine adjuvant with promising results; however, the mechanisms underlying GM-CSF-mediated immune potentiation are incompletely understood. In this study, we investigated the hypothesis that the immune stimulatory role of GM-CSF is in part due to effects on class II MHC Ag presentation. We find that, in primary human monocytes treated for 24–48 h, GM-CSF increases surface class II MHC expression and decreases the relative level of the invariant chain-derived peptide, CLIP, bound to surface class II molecules. GM-CSF also increases expression of the costimulatory molecules CD86 and CD40, but not the differentiation marker CD1a or CD16. Furthermore, GM-CSF-treated monocytes are better stimulators in a mixed leukocyte reaction. Additional analyses of the class II pathway revealed that GM-CSF increases total protein and RNA levels of HLA-DR, DM, and DOα. Expression of class II transactivator (CIITA) types I and III, but not IV, transcripts increases in response to GM-CSF. Furthermore, GM-CSF increases the amount of CIITA associated with the DR promoter. Thus, our data argue that the proinflammatory role of GM-CSF is mediated in part through increased expression of key molecules involved in the class II MHC pathway via induction of CIITA.

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Section: Discussionsupporting

confidence: 55%

Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

Hornell

Beresford

Bushey

et al. 2003

The Journal of Immunology

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“…However, although peritoneal macrophages express far more full length STAT5 than p77/p80, GM-CSF only activates p77/p80 in these cells (Welte et al, 1997). These c-terminally truncated p77 and p80 appear to have distinct properties compared to full length STAT5.…”

Section: Oncogenementioning

confidence: 92%

The role of STATs in myeloid differentiation and leukemia

2000

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“…Mature murine DC express ␥ c and functionally use it for IL-4R type I signaling, as anti-␥ c mAb could affect IL-4 signaling (15). In contrast, IL-4 and IL-13 resulted in strong activation of STAT6 via the IL-4R␣ of both type I and II receptors in mature BM-DC generated with high doses of GM-CSF (16). Recently, the role of IL-4 as a Th1-directing cytokine was strengthened by the observation that IL-12 p70 production by DC is increased by IL-4 (17).…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Differential Functions of IL-4 Receptor Types I and II for Dendritic Cell Maturation and IL-12 Production and Their Dependency on GM-CSF

Lutz¹,

Schnare

Menges³

et al. 2002

The Journal of Immunology

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125

115

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Little is known about the distinct roles of the two types of IL-4R on DC. Here we report that IL-4 and IL-13 are able to promote DC maturation, as evaluated by up-regulation of MHC class II and costimulatory molecules, when the concentration of GM-CSF is relatively lower than the dose of IL-4 or IL-13. In addition, under these conditions both cytokines enable DC to respond to maturation stimuli such as bacterial products or proinflammatory cytokines. Both IL-4 and IL-13 act synergistically with weak maturation stimuli such as TNF-α or CD40. The IL-4R signaling for DC maturation requires the IL-4R α-chain and STAT6, but not Janus kinase 3, indicating that IL-4R type II signaling is preferentially responsible for these effects. In contrast, the production of IL-12 p70, but not IL-10 and TNF, induced by microbial products was enhanced only by IL-4, not by IL-13 or Y119D, a selective type II IL-4R agonist, in vitro and in vivo. This enhancement was dependent on the presence of Janus kinase 3, indicating that this function is exclusively mediated by the type I IL-4R. In short, we discerned the individual roles of the two IL-4R types on DC function, showing that IL-4R type I promotes IL-12 secretion independently of GM-CSF concentration, while IL-4R type II promotes the up-regulation of MHC class II and costimulatory surface markers in a GM-CSF concentration-dependent manner.

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Granulocyte‐macrophage colony‐stimulating factor induces a unique set of STAT factors in murine dendritic cells

Cited by 42 publications

References 32 publications

Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

The role of STATs in myeloid differentiation and leukemia

Differential Functions of IL-4 Receptor Types I and II for Dendritic Cell Maturation and IL-12 Production and Their Dependency on GM-CSF

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