title: Glucocorticoid-induced leucine zipper enhanced expression in dendritic cells is sufficient to drive regulatory T cells expansion in vivo.
abstract: Tolerance induction by dendritic cells (DCs) is, in part, mediated by the activation of regulatory T cells (Tregs). We have previously shown in vitro that human DCs treated with glucocorticoids (GCs), IL-10, or TGF-β upregulate the GC-Induced Leucine Zipper protein (GILZ). GILZ overexpression promotes DC differentiation into regulatory cells that generate IL-10-producing Ag-specific Tregs. To investigate whether these observations extend in vivo, we have generated CD11c-GILZ(hi) transgenic mice. DCs from these mice constitutively overexpress GILZ to levels observed in GC-treated wild-type DCs. In this article, we establish that GILZ(hi) DCs display an accumulation of Foxp3(+) Tregs in the spleens of young CD11c-GILZ(hi) mice. In addition, we show that GILZ(hi) DCs strongly increase the Treg pool in central and peripheral lymphoid organs of aged animals. Upon adoptive transfer to wild-type recipient mice, OVA-loaded GILZ(hi) bone marrow-derived DCs induce a reduced activation and proliferation of OVA-specific T cells as compared with control bone marrow-derived DCs, associated with an expansion of thymus-derived CD25(+)Foxp3(+) CD4 T cells. Transferred OVA-loaded GILZ(hi) DCs produce significantly higher levels of IL-10 and express reduced levels of MHC class II molecules as compared with OVA-loaded control DCs, emphasizing the regulatory phenotype of GILZ(hi) DCs in vivo. Thus, our work demonstrates in vivo that the GILZ overexpression alone is sufficient to promote a tolerogenic mode of function in DCs.
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, 94 275, France;
authors.forename: Joseph
authors.initials: J
authors.lastname: Calmette
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, 94 275, France;
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ellouze
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, 94 275, France;
authors.forename: Thi
authors.initials: T
authors.lastname: Tran
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, 94 275, France;
authors.forename: Soumaya
authors.initials: S
authors.lastname: Karaki
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, 94 275, France;
authors.forename: Emilie
authors.initials: E
authors.lastname: Ronin
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, 94 275, France;
authors.forename: Francis
authors.initials: F
authors.lastname: Capel
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Pharmacie, Université Paris-Sud, Chatenay Malabry, 92 296, France;
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.affiliation: INSERM U996, Clamart, 92 140, France;
authors.forename: Françoise
authors.initials: F
authors.lastname: Bachelerie
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, 94 275, France;
authors.forename: Roman
authors.initials: R
authors.lastname: Krzysiek
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, 94 275, France;
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
authors.affiliation: INSERM U996, Clamart, 92 140, France; Faculté de Médecine, Université Paris-Sud, Le Kremlin Bicêtre, 94 275, France; veronique.godot@gmail.com geraldine.schlecht-louf@u-psud.fr.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Schlecht-Louf
authors.affiliation: INSERM U955, Eq16, Créteil, 94 000, France; Vaccine Research Institute, Créteil, 94 000, France; and Université Paris Est, Faculté de Médecine, Créteil, 94 000, France veronique.godot@gmail.com geraldine.schlecht-louf@u-psud.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Godot
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D007108:Immune Tolerance / Q000235:genetics; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000941:Antigens; D039521:CD11c Antigen; C498608:Dsip1 protein, mouse; D014157:Transcription Factors