STAT3 is required for Flt3L-dependent dendritic cell differentiation.
The signals that control decisions of progenitor commitment involve the interplay of both cytokines and transcription factors. Flt3L has emerged as a potential regulator of dendritic cell (DC) development, but regulation of HSC commitment to the DC lineage remains poorly understood. Our central finding is the identification of STAT3 activation as a checkpoint of Flt3L-regulated DC development. Deletion of STAT3 caused profound deficiency in the DC compartment and abrogated Flt3L effects on DC development. DC derivation by Flt3L revealed a normal HSC pool, a 2- to 3-fold accumulation of CLP/CMP, but absence of common DC precursors as well as their DC progeny in STAT3-deficient mice. The formation of CMP and CLP represents the first decisive lineage commitment step, and in this regard we provide evidence that commitments of CLP/CMP to the DC lineage strictly depend on the interplay of both Flt3L and STAT3 activation.
Laouar
Yasmina
Y
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Welte
Thomas
T
Fu
Xin-Yuan
XY
Flavell
Richard A
RA
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006706:Homeostasis; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000172:deficiency / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C084881:flt3 ligand protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor