Flt3 in Regulation of Type I Interferon-Producing Cell and Dendritic Cell Development

Autor:	Nobuyuki Onai, Markus G. Manz, Michael A. Schmid, Aya Obata-Onai
Rok vydání:	2007
Předmět:	Myeloid Cellular differentiation Cell Biology Ligands Models Biological General Biochemistry Genetics and Molecular Biology fluids and secretions History and Philosophy of Science Downregulation and upregulation Proto-Oncogene Proteins hemic and lymphatic diseases medicine Animals Humans Cell Lineage cardiovascular diseases Progenitor cell Cell Proliferation Cell growth General Neuroscience Gene Expression Regulation Developmental Membrane Proteins Cell Differentiation hemic and immune systems Dendritic Cells Dendritic cell Hematopoietic Stem Cells Up-Regulation Cell biology Haematopoiesis medicine.anatomical_structure Interferon Type I embryonic structures Trans-Activators Signal Transduction
Zdroj:	Annals of the New York Academy of Sciences. 1106:253-261
ISSN:	0077-8923
DOI:	10.1196/annals.1392.015
Popis:	Flt3-ligand is a nonredundant cytokine in type I interferon-producing cell (IPC) and dendritic cell (DC) development. We demonstrated that IPC and DC differentiation potential is confined to Flt3(+)-hematopoietic progenitor cells, that Flt3-ligand drives development along both lymphoid and myeloid developmental pathways from Flt3(+)-progenitors to Flt3(+)-IPCs and -DCs, and that in vivo pharmacologic inhibition of Flt3-signaling leads to disruption of IPC and DC development in spite of consecutive Flt3-ligand upregulation in treated animals. We here summarize our recent findings that overexpression of human Flt3 in Flt3(-) and Flt3(+) hematopoietic progenitors rescues and enhances their IPC and DC differentiation potential, respectively. Based on these data, we propose an instructive, demand-regulated, cytokine-driven IPC and DC regeneration model, where high Flt3-ligand levels initiate a self-sustaining, Flt3-STAT3 and -PU.1-mediated IPC and DC differentiation program in Flt3(+)-hematopoietic progenitor cells.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d80b2f6a0c93296d8ed9cca910d7b44 https://doi.org/10.1196/annals.1392.015 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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