TRPV1 Gates Tissue Access and Sustains Pathogenicity in Autoimmune Encephalitis

Autor: 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
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Molecular Medicine, Vol 19, Iss 1, Pp 149-159 (2013)
Druh dokumentu: article
ISSN: 1076-1551
1528-3658
DOI: 10.2119/molmed.2012.00329
Popis: 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.
Databáze: Directory of Open Access Journals
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