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Flt3 in Regulation of Type I Interferon‐Producing Cell and Dendritic Cell Development
Author(s) -
ONAI NOBUYUKI,
OBATAONAI AYA,
SCHMID MICHAEL A.,
MANZ MARKUS G.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1392.015
Subject(s) - progenitor cell , haematopoiesis , microbiology and biotechnology , dendritic cell , myeloid , cytokine , downregulation and upregulation , biology , chemistry , cancer research , stem cell , immunology , immune system , biochemistry , gene
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.