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 posttranscriptional mechanism. Overall, our findings unveiled a new role for common γ -chain cytokines as a molecular link between autophagy induction and T-cell activation.