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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.

Original publication

DOI

10.2119/molmed.2012.00329

Type

Journal article

Journal

Mol Med

Publication Date

24/07/2013

Volume

19

Pages

149 - 159

Keywords

Adoptive Transfer, Adult, Animals, Brain, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Lymph Nodes, Male, Mice, Mice, Transgenic, Multiple Sclerosis, Myelin-Oligodendrocyte Glycoprotein, Peptide Fragments, Pertussis Toxin, Polymorphism, Single Nucleotide, Spinal Cord, Spleen, TRPV Cation Channels