Referenced in: none

Automatically associated channels: Kv2.1 , TRP , TRPV , TRPV1

Title: TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis.

Authors: Geoffrey Paltser, Xue Jun Liu, Jason Yantha, Shawn Winer, Hubert Tsui, Ping Wu, Yuko Maezawa, Lindsay S Cahill, Christine L Laliberté, Sreeram V Ramagopalan, Gabriele C DeLuca, A Dessa Sadovnick, Igor Astsaturov, George C Ebers, R Mark Henkelman, Michael W Salter, H-Michael Dosch

Journal, date & volume: Mol. Med., 2013 , 19, 149-59

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23689362

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.