Transforming growth factor β1 up‐regulates interferon regulatory factor 8 during dendritic cell development

Ju, Xinsheng; Ruau, David; Jäntti, Piritta; Seré, Kristin; Becker, Christiane; Wiercinska, Eliza; Bartz, C.; Erdmann, Bettina; Dooley, Steven; Zenke, Martin

doi:10.1002/eji.200636504

Cited by 18 publications

(15 citation statements)

References 51 publications

(86 reference statements)

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“…TGF-b1 accelerates DC development and impacts on DC subset specification TGF-b1 signaling is of pivotal importance for DC development (25,38,(61)(62)(63), yet the impact of TGF-b1 signaling on DC subset specification from CDPs has not been analyzed. The in vitro system described in this paper provides an excellent means to decipher molecular events in response to TGF-b1 in CDPs and its consequences.…”

Section: Cdps Show a Gene Expression Pattern Primed For DC Developmentmentioning

confidence: 99%

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TGF-β1 Accelerates Dendritic Cell Differentiation from Common Dendritic Cell Progenitors and Directs Subset Specification toward Conventional Dendritic Cells

Felker

Seré

Lin

et al. 2010

The Journal of Immunology

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Section: Cdps Show a Gene Expression Pattern Primed For DC Developmentmentioning

confidence: 99%

“…The analysis revealed clusters of up-and downregulated genes that contained known TGF-b1 target genes, such as Smad7, Id2, and Irf4 (Supplemental Fig. 6) (24,38,62).…”

Section: Cdps Show a Gene Expression Pattern Primed For DC Developmentmentioning

confidence: 99%

TGF-β1 Accelerates Dendritic Cell Differentiation from Common Dendritic Cell Progenitors and Directs Subset Specification toward Conventional Dendritic Cells

Felker

Seré

Lin

et al. 2010

The Journal of Immunology

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“…Beyond the known cytokine scenario, ECs synthesize multiple other proteins [10], i.e. chemokines of the C-X-C, C-C and TNF receptor superfamily; however, whether these factors can also support hematopoietic progenitor cell (HPC) expansion remains unknown.Notably, microarray technologies monitoring expression changes for thousands of genes have been the basis for several systematic studies of immune and stem cells and their involvement in a variety of processes [11][12][13][14][15]. For example, microarrays of ECs helped to reveal unknown signaling pathways in the endothelial immune cascades [16], specify the role of inflammatory stimuli in neutrophil transmigration [17] and identify the effects of biochemical forces [18].…”

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confidence: 99%

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Moldenhauer

Futschik

et al. 2011

Eur J Immunol

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The identification of soluble factors involved in stem cell renewal is a major goal in the assessment of the BM niche. We have previously shown that human endothelial cell (EC) supernatants can induce the proliferation of hematopoietic progenitor cells (HPCs), especially after stimulation with IL-1b. To identify new potential growth factors, we compared the expression profile of IL-1b-stimulated ECs over 4, 8 and 16 h with non-stimulated ECs using oligonucleotide microarrays covering more than 46 000 transcripts. Most significant changes were detected after 4 h. Utilization of Gene Ontology annotation for the stimulated EC transcriptome indicated multiple upregulated genes encoding extracellular proteins with a cell-cell signaling function. Using flow cytometry, delta, colony and cobblestone assays, we assessed the proliferative capacities of 11 gene products, i.e. IL-8, IL-32, FGF-18, osteoprotegerin, Gro 1-3, ENA78, GCP-2, CCL2 and CCL20, which are not known to induce HPC expansion. Notably, IL-32 and to a lesser degree osteoprotegerin and Gro 3 significantly induced the proliferation of HPCs. Furthermore, IL-32 attenuated chemotherapy-related BM cytotoxicities by increasing the number of HPCs in mice. Our findings confirm that the combination of microarrays and gene annotation helps to identify new hematopoietic growth factors. Keywords: Endothelial cells . Hematopoietic stem cells . Molecular genetics Supporting Information available online IntroductionEndothelial cells (ECs) have been shown to support the proliferation of hematopoietic CD34 1 progenitor cells by the constitutive production of cytokines [1,2]. In previous studies, we demonstrated that ECs stimulated by TNF-a induced the generation of dendritic cells from CD34 1 cells for more than 6 wk [3]. ILs, on the other hand, can also induce the proliferation of hematopoietic and myeloid progenitors [4].So far, GM-CSF and G-CSF are known to be secreted by IL-stimulated ECs [5]. Other endothelial factors propagating progenitor expansion include stem cell factor (SCF) [6] 1774inhibitory factor (LIF) [7] and 9]. Beyond the known cytokine scenario, ECs synthesize multiple other proteins [10], i.e. chemokines of the C-X-C, C-C and TNF receptor superfamily; however, whether these factors can also support hematopoietic progenitor cell (HPC) expansion remains unknown.Notably, microarray technologies monitoring expression changes for thousands of genes have been the basis for several systematic studies of immune and stem cells and their involvement in a variety of processes [11][12][13][14][15]. For example, microarrays of ECs helped to reveal unknown signaling pathways in the endothelial immune cascades [16], specify the role of inflammatory stimuli in neutrophil transmigration [17] and identify the effects of biochemical forces [18]. Microarrays of cultured HPCs also defined detrimental components of engineered extracellular matrices [19]. To use microarrays of feeder cells for the identification of new hematopoietic growth factors is another aspect. Choong e...

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“…20 Upregulation of ICSBP by TGF-b during dendritic cell development is well established. 21 In addition, TGF-b can induce IRF-1, which mediates growth inhibition by TGF-b in human hepatocarcinoma cells. 22 Furthermore, IRF-7 can interact with Smad3, and TGF-b/Smad3 signaling regulates many IRF-7 functions, including induction of IFN-a and -b.…”

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Interferon consensus sequence binding protein-induced cell proliferation is mediated by TGF-β signaling and p38 MAPK activation

Sung

Kim

et al. 2011

Laboratory Investigation

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Interferon consensus sequence binding protein (ICSBP), also known as interferon regulatory factor (IRF)-8, is a member of the interferon (IFN)-g regulatory transcription factors. Studies have suggested a connection between TGF-b signaling and IRFs. Thus, we investigated the effect of ICSBP on transforming growth factor (TGF)-b signaling in HL-60, an acute promyelocytic leukemia cell line. Stable expression of ICSBP in HL-60 cells resulted in strong induction of TGF-b receptor expression and activation of non-Smad as well as Smad pathways. ICSBP expression also augmented cell growth. ICSBP knockdown with small interfering RNA (siRNA) attenuated cell growth and decreased TGF-b receptor I (TGF-bRI) expression. In addition, reduction of TGF-bRI using siRNA or pharmacological inhibitor reduced growth of ICSBP-expressing cells. ICSBP expression also led to increased phosphorylation and activation of Akt and p38 MAPK. However, p38 MAPK, but not PI3K-Akt, inhibition abrogated ICSBP-mediated proliferation. Furthermore, siRNA knockdown of either ICSBP or TGF-bRI resulted in decreased p38 activation. Intriguingly, TGF-b-activated kinase 1 (TAK-1), which phosphorylates p38, was activated in ICSBP-expressing cells and its activity was reduced by TGF-bRI inhibition. Finally, siRNA knockdown of ICSBP or TGF-bRI reduced TAK-1 phosphorylation. This study identifies a novel role for ICSBP in regulating cell growth via TGF-b receptor upregulation and subsequent activation of the TGF-b receptor/TAK-1/p38 pathway.

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Transforming growth factor β1 up‐regulates interferon regulatory factor 8 during dendritic cell development

Cited by 18 publications

References 51 publications

TGF-β1 Accelerates Dendritic Cell Differentiation from Common Dendritic Cell Progenitors and Directs Subset Specification toward Conventional Dendritic Cells

TGF-β1 Accelerates Dendritic Cell Differentiation from Common Dendritic Cell Progenitors and Directs Subset Specification toward Conventional Dendritic Cells

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Interferon consensus sequence binding protein-induced cell proliferation is mediated by TGF-β signaling and p38 MAPK activation

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