title: Cutting edge: Flt3 ligand mediates STAT3-independent expansion but STAT3-dependent activation of myeloid-derived suppressor cells.
abstract: 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.
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;
authors.forename: Brian R
authors.initials: BR
authors.lastname: Rosborough
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Mathews
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Matta
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Dàlia
authors.initials: D
authors.lastname: Raïch-Regué
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
authors.forename: Hēth R
authors.initials: HR
authors.lastname: Turnquist
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology; D016130:Immunophenotyping; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; C084881:flt3 ligand protein