Towards determining the differentiation program of antigen-presenting dendritic cells by transcriptional profiling

Ju, Xinsheng; Hacker, Christine; Madruga, Jaime; Kurz, Steffen M; Knespel, Siegne; Blendinger, Gitta; Rose-John, Stefan; Zenke, Martin

doi:10.1078/0171-9335-00294

Cited by 28 publications

(43 citation statements)

References 49 publications

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“…In this study, we describe a novel two-step culture system for mouse DC where a Flt3 ϩ CD11b ϩ progenitor from mouse bone marrow is first amplified with a specific cytokine combination and then differentiated into fully functional DC with GM-CSF. This approach follows a strategy that we successfully used before for human DC (18,32,56).…”

Section: Discussionmentioning

confidence: 99%

“…27-32, and references therein). DC precursors were first amplified by SCF, FL, Tpo, and hyper-IL-6, and then induced to differentiate into DC by GM-CSF and IL-4 (18,32). Using this culture system, fully functional DC were obtained and used to monitor the changes in gene expression during DC development by DNA microarrays (18,32).…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

“…RNA isolation, cDNA and cRNA synthesis, DNA microarray hybridization and analysis for DC and Flt3 ϩ CD11b ϩ progenitor cells were conducted essentially as described before (18,32). In brief, total RNA was isolated with RNeasy kits including DNase digestion (Qiagen).…”

Section: Rna Isolation and Dna Microarray Analysismentioning

confidence: 99%

“…ϩ CD11b ϩ progenitors and DC at different stages of development were subjected to transcriptional profiling by DNA microarrays to gain new insights into differentially regulated genes involved in the DC differentiation program, thereby applying a strategy that was successfully applied before for human DC (18,32). RNA from Flt3 ϩ CD11b ϩ progenitor cells and DC was prepared and subjected to DNA microarray analysis using Affymetrix GeneChip arrays that contain probe sets for ϳ6000 known genes and ϳ6500 expressed sequence tags.…”

Section: Flt3mentioning

confidence: 99%

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Progressive and Controlled Development of Mouse Dendritic Cells from Flt3+CD11b+ Progenitors In Vitro

Hieronymus

Gust

Kirsch

et al. 2005

The Journal of Immunology

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Dendritic cells (DC) represent key regulators of the immune system, yet their development from hemopoietic precursors is poorly defined. In this study, we describe an in vitro system for amplification of a Flt3+CD11b+ progenitor from mouse bone marrow with specific cytokines. Such progenitor cells develop into both CD11b+ and CD11b− DC, and CD8α+ and CD8α− DC in vivo. Furthermore, with GM-CSF, these progenitors synchronously differentiated into fully functional DC in vitro. This two-step culture system yields homogeneous populations of Flt3+CD11b+ progenitor cells in high numbers and allows monitoring the consecutive steps of DC development in vitro under well-defined conditions. We used phenotypic and functional markers and transcriptional profiling by DNA microarrays to study the Flt3+CD11b+ progenitor and differentiated DC. We report here on an extensive analysis of the surface Ag expression of Flt3+CD11b+ progenitor cells and relate that to surface Ag expression of hemopoietic stem cells. Flt3+CD11b+ progenitors studied exhibit a broad overlap of surface Ags with stem cells and express several stem cell Ags such as Flt3, IL-6R, c-kit/SCF receptor, and CD93/AA4.1, CD133/AC133, and CD49f/integrin α6. Thus, Flt3+CD11b+ progenitors express several stem cell surface Ags and develop into both CD11b+ and CD11b− DC, and CD8α+ and CD8α− DC in vivo, and thus into both of the main conventional DC subtypes.

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Section: Discussionmentioning

confidence: 99%

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Section: Rna Isolation and Dna Microarray Analysismentioning

confidence: 99%

Section: Flt3mentioning

confidence: 99%

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Progressive and Controlled Development of Mouse Dendritic Cells from Flt3+CD11b+ Progenitors In Vitro

Hieronymus

Gust

Kirsch

et al. 2005

The Journal of Immunology

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“…Most of these studies were performed using micro-array analysis and are reviewed elsewhere [54][55][56][57][58][59][60][61][62][63][64][65][66]. With the advent of proteomic approaches, also studies on DCs have been performed at the protein level, resulting in the identification of different proteins that add new information and are complementary to those obtained at the mRNA level.…”

Section: Maturation Process Of Human Dcsmentioning

confidence: 99%

Understanding dendritic cell biology and its role in immunological disorders through proteomic profiling

Ferreira

Mathieu

Overbergh

2010

Proteomics Clinical Apps

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Dendritic cells (DC) have always been present on the bright spot of immune research. They have been extensively studied for the last 35 years, and much is known about their different phenotypes, stimulatory capacity, and role in the immune system. During the last 15 years, great attention has been given to studies on global gene and protein expression profiles during the differentiation and maturation processes of these cells. It is well understood that studying the proteome, together with information on the role of protein post-translational modifications (PTM), will reveal the real dynamics of a living cell. The rapid increase of proteomic studies during the last decade describing the differentiation and maturation process in DCs, as well as modifications brought by the use of different compounds that either increase or decrease their immunogenicity, reflects the importance of understanding the molecular processes behind the functional properties of these cells. In the present review, we will give an overview of proteomic studies focusing on DCs. Thereby we will concentrate on the importance of these studies in understanding DC behavior from a molecular point of view and how these findings have aided in understanding the differences in functional properties of these cells.

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

Ruau

Jäntti

et al. 2007

Eur J Immunol

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Langerhans cells (LC) represent the cutaneous contingent of dendritic cells (DC). Their development critically depends on transforming growth factor b1 (TGF-b1) as demonstrated by analysis of TGF-b1 -/-mice, which lack LC. Here we used a two-step culture system and transcriptional profiling by DNA microarrays to search for TGF-b1 target genes in DC. The study identified interferon regulatory factor 8 (IRF-8) as a novel target gene of TGF-b1 signaling in DC. TGF-b1 effectively induced Smad2/3 phosphorylation and IRF-8 RNA and protein expression. Blocking the TGF-b1/Smad pathway by ectopic expression of inhibitory Smad7 and by SB431542 inhibitor abolished TGF-b1 induced up-regulation of IRF-8. Furthermore, TGF-b1-dependent induction of IRF-8 occurred in the absence of protein biosynthesis, suggesting a direct action of TGF-b1/Smad signaling on IRF-8 gene activity. TGF-b1 also induced expression of the chemokine receptor CCR7 and enhanced DC migration towards CCR7 ligand ELC. DC of IRF-8 -/-mice show reduced CCR7 expression and migratory activity, thereby implicating the TGF-b1/Smad/IRF-8 signaling pathway in CCR7 regulation. Thus, this study identified a novel TGF-b1/Smad/IRF-8 signaling pathway with an impact on DC phenotype and function.

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Towards determining the differentiation program of antigen-presenting dendritic cells by transcriptional profiling

Cited by 28 publications

References 49 publications

Progressive and Controlled Development of Mouse Dendritic Cells from Flt3+CD11b+ Progenitors In Vitro

Progressive and Controlled Development of Mouse Dendritic Cells from Flt3+CD11b+ Progenitors In Vitro

Understanding dendritic cell biology and its role in immunological disorders through proteomic profiling

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

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