jimmun published online 31 October 2014 J Immunol Material Supplementary 8.DCSupplemental.html http://www.jimmunol.org/content/suppl/2014/10/31/jimmunol.140075 Subscriptions http://jimmunol.org/subscriptions is online at: The Journal of Immunology Information about subscribing to Permissions http: 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-b 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 trans-genic 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.