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- W4313355049 abstract "Abstract Introduction: Fms-like tyrosine kinase 3 ligand (Flt3L) promotes dendritic cell (DC) expansion; however, its influence on myeloid-derived suppressor cells (MDSC), an immature population of myeloid cells that suppresses T cell immunity, has not been studied. Methods: BALB/c mice were treated with Flt3L (10 μg/d i.p., 10 d) in the presence or absence of STAT3 inhibitor S31-201 (5 mg/kg/d). Splenic DC and MDSC were isolated by CD11c+ and Gr1+ magnetic bead selection, respectively. Stimulation and suppression of CD3+ T cell responses were assayed by MLR. Syngeneic MDSC were adoptively transferred (5x106) to BALB/c recipients 1 d before C57BL/6 heart transplantation and survival monitored. Results and Conclusions: Flt3L increased MDSC (CD11b+Gr1+) frequency and absolute numbers. MDSC from Flt3L-treated mice potently suppressed CD3+ T cell proliferation greater than control MDSC from naïve splenocytes. Conversely, Flt3L-expanded DC stimulated increased proliferation of allogeneic T cells compared to those from naïve control mice. While STAT3 is considered crucial for MDSC expansion and activation, STAT3 inhibition reduced Flt3L-mediated DC, but not MDSC, expansion. STAT3 inhibition augmented MDSC expansion by Flt3L, without affecting their suppressive capacity. Flt3L-expanded MDSC, but not control MDSC, demonstrated in vivo suppressive activity by prolonging fully MHC-mismatched heart transplant survival. Together, these data identify a novel immunomodulatory function of Flt3L." @default.
- W4313355049 created "2023-01-06" @default.
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- W4313355049 date "2013-05-01" @default.
- W4313355049 modified "2023-10-12" @default.
- W4313355049 title "Flt3 ligand expands and activates myeloid-derived suppressor cells in a STAT3-independent manner (P1074)" @default.
- W4313355049 doi "https://doi.org/10.4049/jimmunol.190.supp.185.11" @default.
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