Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines

• Published in: Blood 2006-02, Vol.107 (3), p.1039-1047
• Main Authors: Cannarile, Lorenza, Fallarino, Francesca, Agostini, Massimiliano, Cuzzocrea, Salvatore, Mazzon, Emanuela, Vacca, Carmine, Genovese, Tiziana, Migliorati, Graziella, Ayroldi, Emira, Riccardi, Carlo
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bleomycin - administration & dosage; Bleomycin - adverse effects; Cell Differentiation - genetics; Cell Differentiation - immunology; Cytokines - immunology; Dexamethasone - administration & dosage; Fundamental and applied biological sciences. Psychology; Fundamental immunology; GATA3 Transcription Factor - immunology; Hypersensitivity, Delayed - genetics; Hypersensitivity, Delayed - immunology; Immunobiology; Immunologic Factors - administration & dosage; Mice; Mice, Transgenic; Modulation of the immune response (stimulation, suppression); Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - immunology; Pulmonary Fibrosis - pathology; STAT6 Transcription Factor - immunology; Th2 Cells - immunology; Transcription Factors - genetics; Transcription Factors - immunology; Transgenes - genetics; Transgenes - immunology; Up-Regulation - genetics; Up-Regulation - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-05-2183

GILZ (glucocorticoid-induced leucine zipper), a gene induced by dexamethasone, is involved in control of T lymphocyte activation and apoptosis. In the present study, using Gilz transgenic mice (TG), which overexpress GILZ in the T-cell lineage, we demonstrate that Gilz is implicated in T helper-2 (Th-2) response development. After in vitro stimulation by CD3/CD28 antibodies, peripheral naive CD4+ T cells from TG mice secrete more Th-2 cytokines such as interleukin-4 (IL-4), IL-5, IL-13, and IL-10, and produce less Th-1 cytokines such as interferon-γ (IFN-γ) than wild-type mice (WT). CD4+ TG lymphocytes up-regulated Th-2 cytokine expression in the specific response to ovalbumin chicken egg (OVA) antigen immunization. Up-regulation correlated with increased expression of GATA-3 and signal transducer and activator of transcription 6 (Stat6), Th-2–specific transcription factors and decreased expression of T-bet, a transcription factor involved in Th-1 differentiation. Finally, in TG mice delayed-type hypersensitivity, a Th-1 response, was inhibited and bleomycin-induced pulmonary fibrosis, a Th-2 mediated disease, was more severe. These results indicate that Gilz contributes to CD4+ commitment toward a Th-2 phenotype and suggest this contribution may be another mechanism accounting for glucocorticoid immunomodulation.