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- W1909971323 abstract "α-Galactosylceramide represents a new class of vaccine adjuvants and immunomodulators that stimulate NKT cells to secrete Th1 and Th2 cytokines. Synthetic variants with short or unsaturated acyl chains exhibit a striking Th2 bias in vivo but no evidence of defect in TCR signaling or stimulation of NKT cells in vitro. Using cd1d1(fl/fl) mice, we demonstrated that distinct APC types explained the cytokine bias in vivo. Whereas NKT stimulation by α-Galactosylceramide required CD1d expression by dendritic cells (DCs), presentation of the Th2 variants was promiscuous and unaffected by DC-specific ablation of CD1d. This DC-independent stimulation failed to activate the feedback loop between DC IL-12 and NK cell IFN-γ, explaining the Th2 bias. Conversely, forced presentation of the Th2 variants by DC induced high IL-12. Thus, lipid structural variations that do not alter TCR recognition can activate distinct Th1 or Th2 cellular networks by changing APC targeting in vivo." @default.
- W1909971323 created "2016-06-24" @default.
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- W1909971323 date "2012-03-05" @default.
- W1909971323 modified "2023-10-11" @default.
- W1909971323 title "Distinct APCs Explain the Cytokine Bias of α-Galactosylceramide Variants In Vivo" @default.
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- W1909971323 doi "https://doi.org/10.4049/jimmunol.1102414" @default.
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