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

Lorenza Cannarile, Francesca Fallarino, Massimiliano Agostini, Salvatore Cuzzocrea, Emanuela Mazzon, Carmine Vacca, Tiziana Genovese, Graziella Migliorati, Emira Ayroldi, Carlo Riccardi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1039-1047
Number of pages9
JournalBlood
Volume107
Issue number3
DOIs
Publication statusPublished - Feb 1 2006

ASJC Scopus subject areas

  • Hematology

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    Cannarile, L., Fallarino, F., Agostini, M., Cuzzocrea, S., Mazzon, E., Vacca, C., Genovese, T., Migliorati, G., Ayroldi, E., & Riccardi, C. (2006). Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines. Blood, 107(3), 1039-1047. https://doi.org/10.1182/blood-2005-05-2183