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PMID: 19523851 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Notch and wingless signaling cooperate in regulation of dendritic cell differentiation.

Immunity ·Vol. 30 ·No. 6 ·2009-06-19 ·Pages 845-59

Zhou J, Cheng P, Youn JI, Cotter MJ, Gabrilovich DI

Abstract

Dendritic cell (DC) differentiation is regulated by stroma via a network of soluble and cell-bound factors. Notch is one of the major elements of this network. Its role in DC differentiation, however, is controversial. Here, we demonstrate that activation of Notch signaling in hematopoietic progenitor cells (HPCs) promoted differentiation of conventional DCs via activation of the canonical Wingless (Wnt) pathway. Inhibition of the Wnt pathway abrogated the effect of Notch on DC differentiation. The fact that activation of the Wnt pathway in Notch-1-deficient embryonic stem cells restored DC differentiation indicates that Wnt signaling is downstream of the Notch pathway in regulating DC differentiation. Notch signaling activated the Wnt pathway in HPCs via expression of multiple members of the Frizzled family of Wnt receptors, which was directly regulated by the CSL (RPB-Jkappa) transcription factor. Thus, these data suggest a model of DC differentiation via cooperation between Wnt and Notch pathways.

MeSH Terms
Adoptive Transfer Animals Cell Differentiation Cell Line Dendritic Cells/cytology Embryonic Stem Cells/cytology,metabolism Female Frizzled Receptors/immunology,metabolism Hematopoietic Stem Cells/cytology,metabolism Humans Intracellular Signaling Peptides and Proteins Membrane Proteins/genetics,metabolism Mice Mice, Inbred C57BL Receptor, Notch1/genetics,metabolism Signal Transduction/immunology Wnt Proteins/immunology,metabolism beta Catenin/immunology,metabolism
Chemicals
Frizzled Receptors Intracellular Signaling Peptides and Proteins Membrane Proteins Receptor, Notch1 Wnt Proteins beta Catenin delta protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhou Jie
Department of Immunology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA.
Cheng Pingyan
Youn Je-In
Cotter Matthew J
Gabrilovich Dmitry I
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43 references, click to expand
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2009.03.021
Published
2009-06-19
Epub
2009-00-11
Pages
845-59
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2700307
Subset
IM
Grants
NCI NIH HHS · R01 CA100062 · United States
NCI NIH HHS · R01 CA100062-05 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1016/j.immuni.2009.03.021 PMC Full Text View journal details
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