Glucocorticoid-Induced Leucine Zipper Protein Controls Macropinocytosis in Dendritic Cells.
Identifieur interne : 001517 ( PubMed/Corpus ); précédent : 001516; suivant : 001518Glucocorticoid-Induced Leucine Zipper Protein Controls Macropinocytosis in Dendritic Cells.
Auteurs : Joseph Calmette ; Matthieu Bertrand ; Mathias Vétillard ; Mehdi Ellouze ; Shaun Flint ; Valérie Nicolas ; Armelle Biola-Vidamment ; Marc Pallardy ; Eric Morand ; Françoise Bachelerie ; Véronique Godot ; Géraldine Schlecht-LoufSource :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2016.
English descriptors
- KwdEn :
- Animals, Antigen Presentation, Antigens (genetics), Antigens (immunology), CD8-Positive T-Lymphocytes (immunology), Dendritic Cells (immunology), Mice, Mice, Transgenic, Pinocytosis (genetics), Pinocytosis (immunology), T-Lymphocytes, Regulatory (immunology), Transcription Factors (genetics), Transcription Factors (immunology).
- MESH :
- chemical , genetics : Antigens, Transcription Factors.
- chemical , immunology : Antigens, Transcription Factors.
- genetics : Pinocytosis.
- immunology : CD8-Positive T-Lymphocytes, Dendritic Cells, Pinocytosis, T-Lymphocytes, Regulatory.
- Animals, Antigen Presentation, Mice, Mice, Transgenic.
Abstract
Ag sampling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs. In vivo, the GILZ-mediated inhibition of Ag uptake is restricted to the CD8α(+) DC subset, which expresses the highest GILZ level among splenic DC subsets. In recently activated DCs, we further establish that GILZ limits p38 MAPK phosphorylation, providing a possible mechanism for GILZ-mediated macropinocytosis control. Finally, our results demonstrate that the modulation of Ag uptake by GILZ does not result in altered Ag presentation to CD4 T cells but impacts the efficiency of cross-presentation to CD8 T cells. Altogether, our results identify GILZ as an endogenous inhibitor of macropinocytosis in DCs, the action of which contributes to the fine-tuning of Ag cross-presentation.
DOI: 10.4049/jimmunol.1600561
PubMed: 27793999
Links to Exploration step
pubmed:27793999Le document en format XML
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<front><div type="abstract" xml:lang="en">Ag sampling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs. In vivo, the GILZ-mediated inhibition of Ag uptake is restricted to the CD8α(+) DC subset, which expresses the highest GILZ level among splenic DC subsets. In recently activated DCs, we further establish that GILZ limits p38 MAPK phosphorylation, providing a possible mechanism for GILZ-mediated macropinocytosis control. Finally, our results demonstrate that the modulation of Ag uptake by GILZ does not result in altered Ag presentation to CD4 T cells but impacts the efficiency of cross-presentation to CD8 T cells. Altogether, our results identify GILZ as an endogenous inhibitor of macropinocytosis in DCs, the action of which contributes to the fine-tuning of Ag cross-presentation.</div>
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<Abstract><AbstractText>Ag sampling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs. In vivo, the GILZ-mediated inhibition of Ag uptake is restricted to the CD8α(+) DC subset, which expresses the highest GILZ level among splenic DC subsets. In recently activated DCs, we further establish that GILZ limits p38 MAPK phosphorylation, providing a possible mechanism for GILZ-mediated macropinocytosis control. Finally, our results demonstrate that the modulation of Ag uptake by GILZ does not result in altered Ag presentation to CD4 T cells but impacts the efficiency of cross-presentation to CD8 T cells. Altogether, our results identify GILZ as an endogenous inhibitor of macropinocytosis in DCs, the action of which contributes to the fine-tuning of Ag cross-presentation.</AbstractText>
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