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.
CITATION STYLE
Seo, Y.-J., Pritzl, C. J., Vijayan, M., Blake, C. R., McClain, M. E., & Hahm, B. (2012). Sphingosine Analogue AAL-R Increases TLR7-Mediated Dendritic Cell Responses via p38 and Type I IFN Signaling Pathways. The Journal of Immunology, 188(10), 4759–4768. https://doi.org/10.4049/jimmunol.1102754
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