TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis
| Autor: | Yuko Maezawa, H.-Michael Dosch, Michael W. Salter, Xue Jun Liu, Gabriele C. DeLuca, R. Mark Henkelman, Lindsay S. Cahill, Hubert Tsui, Jason Yantha, Christine L. Laliberté, Geoffrey Paltser, Shawn Winer, Sreeram V. Ramagopalan, Igor Astsaturov, Ping Wu, A. Dessa Sadovnick, George C. Ebers |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Adoptive cell transfer Encephalomyelitis Autoimmune Experimental Multiple Sclerosis T cell TRPV Cation Channels Mice Transgenic Single-nucleotide polymorphism Polymorphism Single Nucleotide Myelin oligodendrocyte glycoprotein Mice Genetics medicine Animals Humans Molecular Biology Genetics (clinical) Autoimmune encephalitis biology Multiple sclerosis musculoskeletal neural and ocular physiology Experimental autoimmune encephalomyelitis Brain Articles medicine.disease Adoptive Transfer Peptide Fragments Sensory neuron medicine.anatomical_structure Pertussis Toxin Spinal Cord nervous system Immunology biology.protein Molecular Medicine Female Myelin-Oligodendrocyte Glycoprotein lipids (amino acids peptides and proteins) Lymph Nodes Spleen |
| Zdroj: | Molecular medicine (Cambridge, Mass.). 19(1) |
| ISSN: | 1528-3658 1076-1551 |
| Popis: | 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: | OpenAIRE |
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