title: Glucocorticoid-Induced Leucine Zipper Protein Controls Macropinocytosis in Dendritic Cells.
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.
authors: UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France.
authors: Joseph
authors: J
authors: Calmette
authors: UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France.
authors: Matthieu
authors: M
authors: Bertrand
authors: UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France.
authors: Mathias
authors: M
authors: Vétillard
authors: UMR955, Team 16, Institut de Recherche Vaccinal, INSERM, Université Paris Est Créteil, Créteil 94010, France.
authors: Mehdi
authors: 0000-0002-1359-8756
authors: M
authors: Ellouze
authors: Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
authors: Shaun
authors: 0000-0002-5282-9334
authors: S
authors: Flint
authors: Institut Paris-Sud d'Innovation Thérapeutique, SFR-UMS, Chatenay Malabry 92296, France.
authors: Valérie
authors: V
authors: Nicolas
authors: UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Chatenay Malabry 92296, France; and.
authors: Armelle
authors: A
authors: Biola-Vidamment
authors: UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Chatenay Malabry 92296, France; and.
authors: Marc
authors: M
authors: Pallardy
authors: Southern Clinical School, Monash University Faculty of Medicine, Nursing, and Health Sciences, Clayton, Victoria 3168, Australia.
authors: Eric
authors: 0000-0002-9507-3338
authors: E
authors: Morand
authors: UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France.
authors: Françoise
authors: F
authors: Bachelerie
authors: UMR955, Team 16, Institut de Recherche Vaccinal, INSERM, Université Paris Est Créteil, Créteil 94010, France.
authors: Véronique
authors: V
authors: Godot
authors: UMR996-Inflammation, Chimiokines et Immunopathologie, INSERM, Université Paris-Sud, Université Paris-Saclay, Clamart 92140, France; geraldine.schlecht-louf@u-psud.fr.
authors: Géraldine
authors: G
authors: Schlecht-Louf
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010873:Pinocytosis / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D000941:Antigens; C498608:Dsip1 protein, mouse; D014157:Transcription Factors