Sphingosine analogue AAL-R increases TLR7-mediated dendritic cell responses via p38 and type I IFN signaling pathways.
Sphingosine analogue AAL-R increases TLR7-mediated dendritic cell responses via p38 and type I IFN signaling pathways.
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DOI：
10.4049/jimmunol.1102754
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发表时间：
2012-05-15
期刊：
影响因子：
--
通讯作者：
Hahm B
中科院分区：
文献类型：
--
作者：
Seo YJ;Pritzl CJ;Vijayan M;Blake CR;McClain ME;Hahm B
Sphingosine analogs display immunosuppressive activities and thus have therapeutic potential in the treatment of autoimmune diseases. In this study, we investigated the effects of the sphingosine analog 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-I and co-stimulatory 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, since 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 host immune system in particular upon pathogenic infections.
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