TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis.
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 experiment...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2013
|
| _version_ | 1797088310297886720 |
|---|---|
| author | Paltser, G Liu, X Yantha, J Winer, S Tsui, H Wu, P Maezawa, Y Cahill, L Laliberté, C Ramagopalan, S DeLuca, G Sadovnick, A Astsaturov, I Ebers, G Henkelman, R Salter, M Dosch, H |
| author_facet | Paltser, G Liu, X Yantha, J Winer, S Tsui, H Wu, P Maezawa, Y Cahill, L Laliberté, C Ramagopalan, S DeLuca, G Sadovnick, A Astsaturov, I Ebers, G Henkelman, R Salter, M Dosch, H |
| author_sort | Paltser, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:48:11Z |
| format | Journal article |
| id | oxford-uuid:acbca196-42c7-4c25-b4f5-6bc62747464d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:48:11Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:acbca196-42c7-4c25-b4f5-6bc62747464d2022-03-27T03:31:05ZTRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:acbca196-42c7-4c25-b4f5-6bc62747464dEnglishSymplectic Elements at Oxford2013Paltser, GLiu, XYantha, JWiner, STsui, HWu, PMaezawa, YCahill, LLaliberté, CRamagopalan, SDeLuca, GSadovnick, AAstsaturov, IEbers, GHenkelman, RSalter, MDosch, HMultiple 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. |
| spellingShingle | Paltser, G Liu, X Yantha, J Winer, S Tsui, H Wu, P Maezawa, Y Cahill, L Laliberté, C Ramagopalan, S DeLuca, G Sadovnick, A Astsaturov, I Ebers, G Henkelman, R Salter, M Dosch, H TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. |
| title | TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. |
| title_full | TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. |
| title_fullStr | TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. |
| title_full_unstemmed | TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. |
| title_short | TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis. |
| title_sort | trpv1 gates tissue access and sustains pathogenicity in autoimmune encephalitis |
| work_keys_str_mv | AT paltserg trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT liux trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT yanthaj trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT winers trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT tsuih trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT wup trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT maezaway trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT cahilll trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT lalibertec trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT ramagopalans trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT delucag trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT sadovnicka trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT astsaturovi trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT ebersg trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT henkelmanr trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT salterm trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis AT doschh trpv1gatestissueaccessandsustainspathogenicityinautoimmuneencephalitis |