| First Author | Bai L | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 7 | Pages | 3053-61 |
| PubMed ID | 22393151 | Mgi Jnum | J:183087 |
| Mgi Id | MGI:5317471 | Doi | 10.4049/jimmunol.1102414 |
| Citation | Bai L, et al. (2012) Distinct APCs explain the cytokine bias of alpha-galactosylceramide variants in vivo. J Immunol 188(7):3053-61 |
| abstractText | alpha-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 alpha-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-gamma, 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. |
