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The p.Arg63Trp poly...
The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development
- Article/chapterEnglish2011
Publisher, publication year, extent ...
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2011-09-26
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Rockefeller University Press,2011
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:123526753
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http://kipublications.ki.se/Default.aspx?queryparsed=id:123526753URI
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https://doi.org/10.1084/jem.20102191DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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CD4+ regulatory T cells (Treg cells) expressing the transcription factor Foxp3 play a pivotal role in maintaining peripheral tolerance by inhibiting the expansion and function of pathogenic conventional T cells (Tconv cells). In this study, we show that a locus on rat chromosome 9 controls the size of the natural Treg cell compartment. Fine mapping of this locus with interval-specific congenic lines and association experiments using single nucleotide polymorphisms (SNPs) identified a nonsynonymous SNP in the Vav1 gene that leads to the substitution of an arginine by a tryptophan (p.Arg63Trp). This p.Arg63Trp polymorphism is associated with increased proportion and absolute numbers of Treg cells in the thymus and peripheral lymphoid organs, without impacting the size of the Tconv cell compartment. This polymorphism is also responsible for Vav1 constitutive activation, revealed by its tyrosine 174 hyperphosphorylation and increased guanine nucleotide exchange factor activity. Moreover, it induces a marked reduction in Vav1 cellular contents and a reduction of Ca2+ flux after TCR engagement. Together, our data reveal a key role for Vav1-dependent T cell antigen receptor signaling in natural Treg cell development.
Added entries (persons, corporate bodies, meetings, titles ...)
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Casemayou, A
(author)
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Dejean, AS
(author)
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Gaits-Iacovoni, F
(author)
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Pedros, C
(author)
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Bernard, I
(author)
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Lagrange, D
(author)
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Deckert, M
(author)
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Lamouroux, L
(author)
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Jagodic, MKarolinska Institutet
(author)
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Olsson, TKarolinska Institutet
(author)
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Liblau, RS
(author)
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Fournie, GJ
(author)
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Saoudi, A
(author)
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Karolinska Institutet
(creator_code:org_t)
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In:The Journal of experimental medicine: Rockefeller University Press208:11, s. 2183-21911540-95380022-1007
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Colacios, C
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Casemayou, A
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Dejean, AS
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Gaits-Iacovoni, ...
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Pedros, C
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Bernard, I
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Lagrange, D
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Deckert, M
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Lamouroux, L
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Jagodic, M
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Olsson, T
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Liblau, RS
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Fournie, GJ
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Saoudi, A
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Karolinska Institutet