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- W4313383399 abstract "Abstract Acute graft versus host disease (aGVHD) is a severe and often lethal complication of allogeneic bone marrow transplantation (BMT). We found that mice injected with exopolysaccharide (EPS) secreted by a commensal bacterium, Bacillus subtilis, significantly improved survival, reduced weight loss and decreased production of systemic pro-inflammatory cytokines in GVHD mice. We utilized a novel biosensor mouse model to assess the activation of donor T cells in live mice during aGVHD and found that EPS inhibited the activation of alloreactive donor T cells. EPS also inhibited alloreactive T cell activation in mixed lymphocyte reactions (MLR) in vitro and this inhibition required DCs. Treating DCs with EPS led to upregulation of the inhibitory molecule PD-L1 and secretion of the anti-inflammatory cytokine IL-10, characteristic of inhibitory DCs. We determined that EPS induces inhibitory DCs through TLR4, signaling through both MyD88 and TRIF signaling pathways. The inhibition of alloreactive T cells by these inhibitory DCs is mediated by indoleamine 2,3-dioxygenase (IDO). We hypothesized that inhibition of alloreactive donor T cell activation in GVHD mice by EPS is also mediated by DCs and that EPS induces inhibitory DCs in vivo as well as in vitro. The data demonstrate the potential of EPS or EPS-treated DCs as novel reagents for preventing GVHD." @default.
- W4313383399 created "2023-01-06" @default.
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- W4313383399 date "2020-05-01" @default.
- W4313383399 modified "2023-09-27" @default.
- W4313383399 title "Exopolysaccharide from a commensal bacterium ameliorates aGVHD by decreasing alloreactive donor T cell activation" @default.
- W4313383399 doi "https://doi.org/10.4049/jimmunol.204.supp.87.6" @default.
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