Adenomatous Polyposis Coli Defines Treg Differentiation and Anti-inflammatory Function through Microtubule-Mediated NFAT Localization

Abstract : Adenomatous polyposis coli (APC) is a polarity regulator and tumor suppressor associated with familial adenomatous polyposis and colorectal cancer development. Although extensively studied in epithelial transformation, the effect of APC on T lymphocyte activation remains poorly defined. We found that APC ensures T cell receptor-triggered activation through Nuclear Factor of Activated T cells (NFAT), since APC is necessary for NFAT’s nuclear localization in a microtubule-dependent fashion and for NFAT-driven transcription leading to cytokine gene expression. Interestingly, NFAT forms clusters juxtaposed with microtubules. Ultimately, mouse Apc deficiency reduces the presence of NFAT in the nucleus of intestinal regulatory T cells (Tregs) and impairs Treg differentiation and the acquisition of a suppressive phenotype, which is characterized by the production of the anti-inflammatory cytokine IL-10. These findings suggest a dual role for APC mutations in colorectal cancer development, where mutations drive the initiation of epithelial neoplasms and also reduce Treg-mediated suppression of the detrimental inflammation that enhances cancer growth.
Type de document :
Article dans une revue
Cell Reports , Elsevier Inc, 2017, 21 (1), pp.181-194. 〈10.1016/j.celrep.2017.09.020〉
Liste complète des métadonnées

Littérature citée [82 références]  Voir  Masquer  Télécharger

https://hal.archives-ouvertes.fr/hal-01614654
Contributeur : Vincenzo Di Bartolo <>
Soumis le : mercredi 11 octobre 2017 - 11:17:23
Dernière modification le : mardi 14 novembre 2017 - 15:22:02

Fichier

mmc9.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Citation

Sonia Agüera-Gonzalez, Oliver T. Burton, Elena Vázquez-Chávez, Céline Cuche, Floriane Herit, et al.. Adenomatous Polyposis Coli Defines Treg Differentiation and Anti-inflammatory Function through Microtubule-Mediated NFAT Localization. Cell Reports , Elsevier Inc, 2017, 21 (1), pp.181-194. 〈10.1016/j.celrep.2017.09.020〉. 〈hal-01614654〉

Partager

Métriques

Consultations de la notice

113

Téléchargements de fichiers

18