title: Common γ-chain cytokine signaling is required for macroautophagy induction during CD4+ T-cell activation.
abstract: Macroautophagy is a cellular process that mediates degradation in the lysosome of cytoplasmic components including proteins and organelles. Previous studies have shown that macroautophagy is induced in activated T cells to regulate organelle homeostasis and the cell's energy metabolism. However, the signaling pathways that initiate and regulate activation-induced macroautophagy in T cells have not been identified. Here, we show that activation-induced macroautophagy in T cells depends on signaling from common γ-chain cytokines. Consequently, inhibition of signaling through JAK3, induced downstream of cytokine receptors containing the common γ-chain, prevents full induction of macroautophagy in activated T cells. Moreover, we found that common γ-chain cytokines are not only required for macroautophagy upregulation during T cell activation but can themselves induce macroautophagy. Our data also show that macroautophagy induction in T cells is associated with an increase of LC3 expression that is mediated by a post-transcriptional mechanism. Overall, our findings unveiled a new role for common γ-chain cytokines as a molecular link between autophagy induction and T-cell activation.
authors.affiliation: a Department of Pathology, Albert Einstein College of Medicine ; Bronx , NY USA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Botbol
authors.affiliation: a Department of Pathology, Albert Einstein College of Medicine ; Bronx , NY USA.
authors.forename: Bindi
authors.initials: B
authors.lastname: Patel
authors.affiliation: a Department of Pathology, Albert Einstein College of Medicine ; Bronx , NY USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Macian
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology*; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D016207:Cytokines
keywords: JAK; T cell; common γ-chain; interleukin 2; macroautophagy