Dataset Information

Common ?-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 ?-chain cytokines. Consequently, inhibition of signaling through JAK3, induced downstream of cytokine receptors containing the common ?-chain, prevents full induction of macroautophagy in activated T cells. Moreover, we found that common ?-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 ?-chain cytokines as a molecular link between autophagy induction and T-cell activation.

SUBMITTER: Botbol Y

PROVIDER: S-EPMC4824584 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Common γ-chain cytokine signaling is required for macroautophagy induction during CD4+ T-cell activation.

Botbol Yair Y Patel Bindi B Macian Fernando F

Autophagy 20150101 10

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 signali ...[more]

PMID: 26391567

Similar Datasets

Project description:IntroductionCytokines of the common γ chain (γc) family are critical for the development, differentiation, and survival of T lineage cells. Cytokines play key roles in immunodeficiencies, autoimmune diseases, allergies, and cancer. Although γc is considered an assistant receptor to transmit cytokine signals and is an indispensable receptor in the immune system, its regulatory mechanism is not yet well understood.ObjectiveThis study focused on the molecular mechanisms that γc expression in T cells is regulated under T cell receptor (TCR) stimulation.MethodsThe γc expression in TCR-stimulated T cells was determined by flow cytometry, western blot and quantitative RT-PCR. The regulatory mechanism of γc expression in activated T cells was examined by promoter-luciferase assay and chromatin immunoprecipitation assays. NFAT1 and NFκB deficient cells generated using CRISPR-Cas9 and specific inhibitors were used to examine their role in regulation of γc expression. Specific binding motif was confirmed by γc promotor mutant cells generated using CRISPR-Cas9. IL-7TgγcTg mice were used to examine regulatory role of γc in cytokine signaling.ResultsWe found that activated T cells significantly upregulated γc expression, wherein NFAT1 and NFκB were key in transcriptional upregulation via T cell receptor stimulation. Also, we identified the functional binding site of the γc promoter and the synergistic effect of NFAT1 and NFκB in the regulation of γc expression. Increased γc expression inhibited IL-7 signaling and rescued lymphoproliferative disorder in an IL-7Tg animal model, providing novel insights into T cell homeostasis.ConclusionOur results indicate functional cooperation between NFAT1 and NFκB in upregulating γc expression in activated T cells. As γc expression also regulates γc cytokine responsiveness, our study suggests that γc expression should be considered as one of the regulators in γc cytokine signaling and the development of T cell immunotherapies. Video Abstract.

Dataset Information

Common ?-chain cytokine signaling is required for macroautophagy induction during CD4+ T-cell activation.

Publications

Common γ-chain cytokine signaling is required for macroautophagy induction during CD4+ T-cell activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets