Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

Learn about the flu shot, COVID-19 vaccine, and our masking policy »

Stanford Health Care

Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation. Nature immunology Garris, C. S., Wu, L., Acharya, S., Arac, A., Blaho, V. A., Huang, Y., Moon, B. S., Axtell, R. C., Ho, P. P., Steinberg, G. K., Lewis, D. B., Sobel, R. A., Han, D. K., Steinman, L., Snyder, M. P., Hla, T., Han, M. H. 2013; 14 (11): 1166-1172

Abstract

Sphingosine 1-phosphate (S1P) signaling regulates lymphocyte egress from lymphoid organs into systemic circulation. The 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 an S1pr1 gene encoding phosphorylation-deficient receptors (S1P1(S5A)) developed severe experimental autoimmune encephalomyelitis (EAE) due to autoimmunity mediated by interleukin 17 (IL-17)-producing helper T cells (TH17 cells) in the peripheral immune and nervous system. S1P1 directly activated the Jak-STAT3 signal-transduction pathway via IL-6. Impaired S1P1 phosphorylation enhances TH17 polarization and exacerbates autoimmune neuroinflammation. These mechanisms may be pathogenic in MS.

View details for DOI 10.1038/ni.2730

View details for PubMedID 24076635