Regulation of dendritic cell differentiation and subset distribution by the zinc finger protein CTCF

Abstract The molecular mechanisms that regulate DC differentiation and subset distribution are largely unknown. In this study we report the identification of the C2 H2 zinc finger transcription factors (TF) CTCF as a regulator of DC differentiation. CTCF was expressed in human and murine DC and its...

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Veröffentlicht in:Immunology Letters 2007-04, Vol.109 (2), p.165-174
Hauptverfasser: Koesters, Christina, Unger, Bernd, Bilic, Ivan, Schmidt, Uwe, Bluml, Stefan, Lichtenberger, Beate, Schreiber, Martin, Stockl, Johannes, Ellmeier, Wilfried
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container_end_page 174
container_issue 2
container_start_page 165
container_title Immunology Letters
container_volume 109
creator Koesters, Christina
Unger, Bernd
Bilic, Ivan
Schmidt, Uwe
Bluml, Stefan
Lichtenberger, Beate
Schreiber, Martin
Stockl, Johannes
Ellmeier, Wilfried
description Abstract The molecular mechanisms that regulate DC differentiation and subset distribution are largely unknown. In this study we report the identification of the C2 H2 zinc finger transcription factors (TF) CTCF as a regulator of DC differentiation. CTCF was expressed in human and murine DC and its expression was downregulated during the differentiation of human monocyte-derived DC. Enforced expression of CTCF during the differentiation of murine BM-derived DC (BMDC) caused increased apoptosis and reduced proliferation leading to a dramatically reduced number of CTCF transduced DC. The CTCF expressing BMDC that developed had a more immature phenotype than control cells, and showed defects in maturation upon TLR stimulation. Furthermore, in vivo expression of CTCF led to an increase in the percentage of plasmacytoid DC (pDC) within the DC lineage. Our data provide new insight into molecular mechanisms regulating DC differentiation and subset development and identify CTCF as a factor involved in the regulation of these important processes.
doi_str_mv 10.1016/j.imlet.2007.02.006
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subjects Allergy and Immunology
Animals
Bone Marrow Cells - cytology
Bone Marrow Cells - immunology
CCCTC-Binding Factor
Cell differentiation
Cell Differentiation - immunology
Cell Growth Processes - immunology
Cell Survival - immunology
Dendritic cells
Dendritic Cells - cytology
Dendritic Cells - immunology
Dendritic Cells - metabolism
DNA-Binding Proteins - biosynthesis
DNA-Binding Proteins - immunology
Down-Regulation
Humans
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Repressor Proteins - biosynthesis
Repressor Proteins - immunology
Toll-Like Receptors - immunology
Toll-Like Receptors - metabolism
Transcription factors
Transcription Factors - genetics
Zinc Fingers
title Regulation of dendritic cell differentiation and subset distribution by the zinc finger protein CTCF
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