| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Tran, Thi Pallardy, Marc Ronin, Emilie Karaki, Soumaya Krzysiek, Roman Godot, Véronique Bachelerie, Françoise Schlecht-Louf, Géraldine Capel, Francis Ellouze, Mehdi Emilie, Dominique Calmette, Joseph |
| Description |
Author Affiliation: Calmette J ( INSERM U996, Clamart, 92 140, France); Ellouze M ( INSERM U996, Clamart, 92 140, France); Tran T ( INSERM U996, Clamart, 92 140, France); Karaki S ( INSERM U996, Clamart, 92 140, France); Ronin E ( INSERM U996, Clamart, 92 140, France); Capel F ( INSERM U996, Clamart, 92 140, France); Pallardy M ( INSERM U996, Clamart, 92 140, France); Bachelerie F ( INSERM U996, Clamart, 92 140, France); Krzysiek R ( INSERM U996, Clamart, 92 140, France); Emilie D ( INSERM U996, Clamart, 92 140, France); Schlecht-Louf G ( INSERM U996, Clamart, 92 140, France); Godot V ( INSERM U955, Eq16, Créteil, 94 000, France) |
| 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-ß 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. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
12 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-12-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Dendritic Cells Metabolism Gene Expression T-lymphocytes, Regulatory Transcription Factors Genetics Animals Antigen Presentation Immunology Antigens Antigens, Cd11c Immune Tolerance Immunophenotyping Lymphocyte Activation Lymphocyte Count Lymphocyte Subsets Lymphoid Tissue Mice Mice, Transgenic Phenotype Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
