Sphingosine Analogue AAL-R Increases TLR7-Mediated Dendritic Cell Responses via p38 and Type I IFN Signaling Pathwaysopen access
- Authors
- Seo, Young-Jin; Pritzl, Curtis J.; Vijayan, Madhuvanthi; Blake, Celeste R.; McClain, Mariah E.; Hahm, Bumsuk
- Issue Date
- May-2012
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Citation
- JOURNAL OF IMMUNOLOGY, v.188, no.10, pp 4759 - 4768
- Pages
- 10
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Volume
- 188
- Number
- 10
- Start Page
- 4759
- End Page
- 4768
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/57762
- DOI
- 10.4049/jimmunol.1102754
- ISSN
- 0022-1767
1550-6606
- Abstract
- 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 CD84(+) 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. The Journal of Immunology, 2012, 188: 4759-4768.
- Files in This Item
-
- Appears in
Collections - College of Natural Sciences > Department of Life Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.