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2014 ; 192
(8
): 3470-3
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Cutting edge: Flt3 ligand mediates STAT3-independent expansion but
STAT3-dependent activation of myeloid-derived suppressor cells
#MMPMID24639346
Rosborough BR
; Mathews LR
; Matta BM
; Liu Q
; Raïch-Regué D
; Thomson AW
; Turnquist HR
J Immunol
2014[Apr]; 192
(8
): 3470-3
PMID24639346
show ga
The Flt3-Flt3 ligand (Flt3L) pathway is critically involved in the
differentiation and homeostasis of myeloid cells, including dendritic cells (DC);
however, its role in the expansion and function of myeloid-derived suppressor
cells (MDSC) has not been determined. In this article, we describe the ability of
Flt3L to expand and activate murine MDSC capable of suppressing allograft
rejection upon adoptive transfer. Although Flt3L expands and augments the
stimulatory capacity of myeloid DC, MDSC expanded by Flt3L have increased
suppressive activity. Although STAT3 is considered the central transcription
factor for MDSC expansion, inhibition and genetic ablation of STAT3 did not
block, but rather augmented, Flt3L-mediated MDSC expansion. MDSC suppressive
function, preserved when STAT3 inhibition was removed, was reduced by genetic
STAT3 deletion. Both STAT3 inhibition and deletion reduced Flt3L-mediated DC
expansion, signifying that STAT3 had reciprocal effects on suppressive MDSC and
immunostimulatory DC expansion. Together, these findings enhance our
understanding of the immunomodulatory properties of Flt3L.