Selective degradation of PU.1 during autophagy represses the differentiation and antitumour activity of TH9 cells

Abstract : Autophagy, a catabolic mechanism that involves degradation of cellular components, is essential for cell homeostasis. Although autophagy favours the lineage stability of regulatory T cells, the contribution of autophagy to the differentiation of effector CD4 T cells remains unclear. Here we show that autophagy selectively represses T helper 9 (TH9) cell differentiation. CD4 T cells lacking Atg3 or Atg5 have increased interleukin-9 (IL-9) expression upon differentiation into TH9 cells relative to Atg3- or Atg5-expressing control cells. In addition, the TH9 cell transcription factor, PU.1, undergoes K63 ubiquitination and degradation through p62-dependent selective autophagy. Finally, the blockade of autophagy enhances TH9 cell anticancer functions in vivo, and mice with T cell-specific deletion of Atg5 have reduced tumour outgrowth in an IL-9-dependent manner. Overall, our findings reveal an unexpected function of autophagy in the modulation of TH9 cell differentiation and antitumour activity, and prompt potential autophagy-dependent modulations of TH9 activity for cancer immunotherapy.Autophagy is a cellular process for recycling cell constituents, and is essential for T cell activation, but its function in T cell polarization is still unclear. Here the authors show that autophagy induces the degradation of transcription factor PU.1 to negatively modulate TH9 homeostasis and antitumour immunity.
Type de document :
Article dans une revue
Nature Communications, Nature Publishing Group, 2017, 8, pp.559. 〈https://www.nature.com/articles/s41467-017-00468-w〉
Liste complète des métadonnées

https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01598895
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : samedi 30 septembre 2017 - 11:20:59
Dernière modification le : vendredi 8 juin 2018 - 14:50:25

Identifiants

  • HAL Id : hal-01598895, version 1

Collections

Citation

Vargas Thaiz Rivera, Cai Zhijian, Shen Yingying, Dosset Magalie, Benoit-Lizon Isis, et al.. Selective degradation of PU.1 during autophagy represses the differentiation and antitumour activity of TH9 cells. Nature Communications, Nature Publishing Group, 2017, 8, pp.559. 〈https://www.nature.com/articles/s41467-017-00468-w〉. 〈hal-01598895〉

Partager

Métriques

Consultations de la notice

69