Selective degradation of PU.1 during autophagy represses the differentiation and antitumour activity of TH9 cells - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2017

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

Résumé

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.

Domaines

Cancer Immunologie

Dates et versions

hal-01598895 , version 1 (30-09-2017)

Identifiants

Citer

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, 2017, 8, pp.559. ⟨10.1038/s41467-017-00468-w⟩. ⟨hal-01598895⟩
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