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Estrogen receptor signaling promotes dendritic cell differentiation by increasing expression of the transcription factor IRF4

 Esther Carreras  ;  Sean Turner  ;  Mark Barton Frank  ;  Nicholas Knowlton  ;  Jeanette Osban  ;  Michael Centola  ;  Chae Gyu Park  ;  Amie Simmons  ;  José Alberola-Ila  ;  Susan Kovats 
 BLOOD, Vol.115(2) : 238-246, 2010 
Journal Title
Issue Date
Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/immunology ; Bone Marrow Cells/metabolism ; CD11b Antigen/genetics ; CD11b Antigen/immunology ; CD11b Antigen/metabolism ; Cell Differentiation/drug effects ; Cell Differentiation/physiology* ; Cells, Cultured ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Dendritic Cells/metabolism* ; Estradiol/pharmacology ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/immunology ; Estrogen Receptor alpha/metabolism* ; Estrogens/pharmacology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/physiology* ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Interferon Regulatory Factors/biosynthesis* ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/immunology ; Mice ; Mice, Mutant Strains ; Myeloid Cells/cytology ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Retroviridae ; Signal Transduction/drug effects ; Signal Transduction/physiology* ; Transduction, Genetic
During inflammation, elevated granulocyte macrophage-colony-stimulating factor (GM-CSF) directs the development of new dendritic cells (DCs). This pathway is influenced by environmental factors, and we previously showed that physiologic levels of estradiol, acting through estrogen receptor alpha (ERalpha), promote the GM-CSF-mediated differentiation of a CD11b(+) DC subset from myeloid progenitors (MPs). We now have identified interferon regulatory factor 4 (IRF4), a transcription factor induced by GM-CSF and critical for CD11b(+) DC development in vivo, as a target of ERalpha signaling during this process. In MPs, ERalpha potentiates and sustains GM-CSF induction of IRF4. Furthermore, retroviral delivery of the Irf4 cDNA to undifferentiated ERalpha(-/-) bone marrow cells restored the development of the estradiol/ERalpha-dependent DC population, indicating that an elevated amount of IRF4 protein substitutes for ERalpha signaling. Thus at an early stage in the MP response to GM-CSF, ERalpha signaling induces an elevated amount of IRF4, which leads to a developmental program underlying CD11b(+) DC differentiation
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
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