| First Author | Seo YJ | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 10 | Pages | 4759-68 |
| PubMed ID | 22490865 | Mgi Jnum | J:188687 |
| Mgi Id | MGI:5441432 | Doi | 10.4049/jimmunol.1102754 |
| Citation | Seo YJ, et al. (2012) Sphingosine analogue AAL-R increases TLR7-mediated dendritic cell responses via p38 and type I IFN signaling pathways. J Immunol 188(10):4759-68 |
| abstractText | Sphingosine analogues display immunosuppressive activities and thus have therapeutic potential in the treatment of autoimmune diseases. In this study, we investigated the effects of the sphingosine analogue AAL-R (FTY720 derivative) on dendritic cell (DC) response upon TLR stimulation. Unlike its known immunosuppressive activity, AAL-R increased TLR7-mediated DC responses by elevating the levels of MHC class I and costimulatory molecules and type I IFN expression and by enhancing the capacity of DCs to induce CD8(+) T cell proliferation. Importantly, the stimulatory activity of AAL-R was dependent on type I IFN signaling, as type I IFN receptor-deficient DCs failed to respond to AAL-R. Also, AAL-R activated p38 MAPK to increase type I IFN synthesis and TLR7-mediated DC maturation. These findings enhance our understanding of sphingosine regulation of the host immune system, in particular upon pathogenic infections. |
