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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 3
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pubmed:dateCreated |
2011-2-28
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pubmed:abstractText |
The tyrosine kinase 2 variant rs34536443 has been established as a genetic risk factor for multiple sclerosis in a variety of populations. However, the functional effect of this variant on disease pathogenesis remains unclear. This study replicated the genetic association of tyrosine kinase 2 with multiple sclerosis in a cohort of 1366 French patients and 1802 controls. Furthermore, we assessed the functional consequences of this polymorphism on human T lymphocytes by comparing the reactivity and cytokine profile of T lymphocytes isolated from individuals expressing the protective TYK2(GC) genotype with the disease-associated TYK2(GG) genotype. Our results demonstrate that the protective C allele infers decreased tyrosine kinase 2 activity, and this reduction of activity is associated with a shift in the cytokine profile favouring the secretion of Th2 cytokines. These findings suggest that the rs34536443 variant effect on multiple sclerosis susceptibility might be mediated by deviating T lymphocyte differentiation toward a Th2 phenotype. This impact of tyrosine kinase 2 on effector differentiation is likely to be of wider importance because other autoimmune diseases also have been associated with polymorphisms within tyrosine kinase 2. The modulation of tyrosine kinase 2 activity might therefore represent a new therapeutic approach for the treatment of autoimmune diseases.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1460-2156
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pubmed:author |
pubmed-author:BrassatDavidD,
pubmed-author:BucciarelliFlorenceF,
pubmed-author:ClanetMichelM,
pubmed-author:ComabellaManuelM,
pubmed-author:ConfavreuxChristianC,
pubmed-author:Cournu-RebeixIsabelleI,
pubmed-author:CouturierNicolasN,
pubmed-author:DebouverieMarcM,
pubmed-author:DeferGillesG,
pubmed-author:EdanGillesG,
pubmed-author:FontaineBertrandB,
pubmed-author:GoertschesRobert HRH,
pubmed-author:Lebrun-FrenayChristineC,
pubmed-author:LiblauRoland SRS,
pubmed-author:Müller-MyhsokBertramB,
pubmed-author:MarsLennart TLT,
pubmed-author:MontalbanXavierX,
pubmed-author:MoreauThibaultT,
pubmed-author:NurtdinovRamil NRN,
pubmed-author:OksenbergJorge RJR,
pubmed-author:RieckmannPeterP,
pubmed-author:SaoudiAbdelhadiA,
pubmed-author:VukusicSandraS,
pubmed-author:WeberFrankF,
pubmed-author:ZettlUwe KUK
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pubmed:issnType |
Electronic
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pubmed:volume |
134
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
693-703
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pubmed:meshHeading |
pubmed-meshheading:21354972-Adolescent,
pubmed-meshheading:21354972-Adult,
pubmed-meshheading:21354972-Case-Control Studies,
pubmed-meshheading:21354972-Cell Proliferation,
pubmed-meshheading:21354972-Cells, Cultured,
pubmed-meshheading:21354972-Chi-Square Distribution,
pubmed-meshheading:21354972-Cytokines,
pubmed-meshheading:21354972-Female,
pubmed-meshheading:21354972-Flow Cytometry,
pubmed-meshheading:21354972-France,
pubmed-meshheading:21354972-GATA3 Transcription Factor,
pubmed-meshheading:21354972-Gene Expression Regulation,
pubmed-meshheading:21354972-Genetic Predisposition to Disease,
pubmed-meshheading:21354972-Genotype,
pubmed-meshheading:21354972-Humans,
pubmed-meshheading:21354972-Male,
pubmed-meshheading:21354972-Models, Molecular,
pubmed-meshheading:21354972-Multiple Sclerosis,
pubmed-meshheading:21354972-Polymorphism, Single Nucleotide,
pubmed-meshheading:21354972-Signal Transduction,
pubmed-meshheading:21354972-T-Lymphocytes,
pubmed-meshheading:21354972-TYK2 Kinase,
pubmed-meshheading:21354972-Time Factors,
pubmed-meshheading:21354972-Young Adult
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pubmed:year |
2011
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pubmed:articleTitle |
Tyrosine kinase 2 variant influences T lymphocyte polarization and multiple sclerosis susceptibility.
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pubmed:affiliation |
INSERM U563 and Pôle des neurosciences, University of Toulouse 3, 31000 Toulouse, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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