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Control of peripheral tolerance by regulatory T cell-intrinsic Notch signaling.

Identifieur interne : 000D24 ( Main/Exploration ); précédent : 000D23; suivant : 000D25

Control of peripheral tolerance by regulatory T cell-intrinsic Notch signaling.

Auteurs : Louis-Marie Charbonnier [États-Unis] ; Sen Wang [États-Unis] ; Peter Georgiev [États-Unis] ; Esen Sefik [États-Unis] ; Talal A. Chatila [États-Unis]

Source :

RBID : pubmed:26437242

Descripteurs français

English descriptors

Abstract

Receptors of the Notch family direct the differentiation of helper T cell subsets, but their influence on regulatory T cell (T(reg) cell) responses is obscure. We found here that lineage-specific deletion of components of the Notch pathway enhanced T(reg) cell-mediated suppression of type 1 helper T cell (T(H)1 cell) responses and protected against their T(H)1 skewing and apoptosis. In contrast, expression in T(reg) cells of a gain-of-function transgene encoding the Notch1 intracellular domain resulted in lymphoproliferation, exacerbated T(H)1 responses and autoimmunity. Cell-intrinsic canonical Notch signaling impaired T(reg) cell fitness and promoted the acquisition by T(reg) cells of a T(H)1 cell-like phenotype, whereas non-canonical Notch signaling dependent on the adaptor Rictor activated the kinase AKT-transcription factor Foxo1 axis and impaired the epigenetic stability of Foxp3. Our findings establish a critical role for Notch signaling in controlling peripheral T(reg) cell function.

DOI: 10.1038/ni.3288
PubMed: 26437242
PubMed Central: PMC4618075


Affiliations:


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Le document en format XML

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<term>Mutation (MeSH)</term>
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<term>Receptor, Notch1 (immunology)</term>
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<term>Lymphocytes auxiliaires Th1 (immunologie)</term>
<term>Maladie du greffon contre l'hôte (immunologie)</term>
<term>Maladie du greffon contre l'hôte (prévention et contrôle)</term>
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<term>Protéines de fusion recombinantes (génétique)</term>
<term>Protéines de fusion recombinantes (immunologie)</term>
<term>Protéines de transport (génétique)</term>
<term>Protéines de transport (immunologie)</term>
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<term>Récepteur Notch1 (génétique)</term>
<term>Récepteur Notch1 (immunologie)</term>
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<term>Souris de lignée C57BL (MeSH)</term>
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<term>Souris transgéniques (MeSH)</term>
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<term>Maladie du greffon contre l'hôte</term>
<term>Protéines de fusion recombinantes</term>
<term>Protéines de transport</term>
<term>Récepteur Notch1</term>
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<term>Mâle</term>
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<term>Souris knockout</term>
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<div type="abstract" xml:lang="en">Receptors of the Notch family direct the differentiation of helper T cell subsets, but their influence on regulatory T cell (T(reg) cell) responses is obscure. We found here that lineage-specific deletion of components of the Notch pathway enhanced T(reg) cell-mediated suppression of type 1 helper T cell (T(H)1 cell) responses and protected against their T(H)1 skewing and apoptosis. In contrast, expression in T(reg) cells of a gain-of-function transgene encoding the Notch1 intracellular domain resulted in lymphoproliferation, exacerbated T(H)1 responses and autoimmunity. Cell-intrinsic canonical Notch signaling impaired T(reg) cell fitness and promoted the acquisition by T(reg) cells of a T(H)1 cell-like phenotype, whereas non-canonical Notch signaling dependent on the adaptor Rictor activated the kinase AKT-transcription factor Foxo1 axis and impaired the epigenetic stability of Foxp3. Our findings establish a critical role for Notch signaling in controlling peripheral T(reg) cell function.</div>
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