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- Title
TRPV1 Gates Tissue Access and Sustains Pathogenicity in Autoimmune Encephalitis.
- Authors
Paltser, Geoffrey; Xue Jun Liu; Yantha, Jason; Winer, Shawn; Hubert Tsui; Ping Wu; Yuko Maezawa; Cahill, Lindsay S.; Laliberté, Christine L.; Ramagopalan, Sreeram V.; DeLuca, Gabriele C.; Sadovnick, A. Dessa; Astsaturov, Igor; Ebers, George C.; Henkelman, R. Mark; Salter, Michael W.; Dosch, H.-Michael
- Abstract
Multiple sclerosis (MS) is a chronic progressive, demyelinating condition whose therapeutic needs are unmet, and whose pathoetiology is elusive. We report that transient receptor potential vanilloid-1 (TRPV1) expressed in a major sensory neuron subset, controls severity and progression of experimental autoimmune encephalomyelitis (EAE) in mice and likely in primary progressive MS. TRPV1–/– B6 congenics are protected from EAE. Increased survival reflects reduced central nervous systems (CNS) infiltration, despite indistinguishable T cell autoreactivity and pathogenicity in the periphery of TRPV1-sufficient and -deficient mice. The TRPV1+ neurovascular complex defining the blood-CNS barriers promoted invasion of pathogenic lymphocytes without the contribution of TRPV1-dependent neuropeptides such as substance P. In MS patients, we found a selective risk-association of the missense rs877610 TRPV1 single nucleotide polymorphism (SNP) in primary progressive disease. Our findings indicate that TRPV1 is a critical disease modifier in EAE, and we identify a predictor of severe disease course and a novel target for MS therapy.
- Publication
Molecular Medicine, 2013, Vol 19, Issue 1, p149
- ISSN
1076-1551
- Publication type
Article
- DOI
10.2119/molmed.2012.00329