Defective sphingosine-1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation
View/ Open
Author
Wu, Linfeng
Acharya, Swati
Arac, Ahmet
Blaho, Victoria A.
Huang, Yingxiang
Moon, Byoung San
Axtell, Robert C.
Ho, Peggy P.
Steinberg, Gary K.
Lewis, David B.
Sobel, Raymond A.
Han, David K.
Steinman, Lawrence
Snyder, Michael P.
Hla, Timothy
Han, May H.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/ni.2730Metadata
Show full item recordCitation
Garris, C. S., L. Wu, S. Acharya, A. Arac, V. A. Blaho, Y. Huang, B. S. Moon, et al. 2014. “Defective sphingosine-1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation.” Nature immunology 14 (11): 1166-1172. doi:10.1038/ni.2730. http://dx.doi.org/10.1038/ni.2730.Abstract
Sphingosine-1-phosphate (S1P) signaling regulates lymphocyte egress from lymphoid organs into systemic circulation. Sphingosine phosphate receptor 1 (S1P1) agonist, FTY-720 (Gilenya™) arrests immune trafficking and prevents multiple sclerosis (MS) relapses. However, alternative mechanisms of S1P-S1P1 signaling have been reported. Phosphoproteomic analysis of MS brain lesions revealed S1P1 phosphorylation on S351, a residue crucial for receptor internalization. Mutant mice harboring a S1pr1 gene encoding phosphorylation-deficient receptors [S1P1(S5A)] developed severe experimental autoimmune encephalomyelitis (EAE) due to T helper (TH) 17-mediated autoimmunity in the peripheral immune and nervous system. S1P1 directly activated Janus-like kinase–signal transducer and activator of transcription 3 (JAK-STAT3) pathway via interleukin 6 (IL-6). Impaired S1P1 phosphorylation enhances TH17 polarization and exacerbates autoimmune neuroinflammation. These mechanisms may be pathogenic in MS.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014310/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406821
Collections
- FAS Scholarly Articles [18256]
- HMS Scholarly Articles [17917]
Contact administrator regarding this item (to report mistakes or request changes)