Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines.
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-gamma (IFN-gamma) 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.
Cannarile
Lorenza
L
Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
Fallarino
Francesca
F
Agostini
Massimiliano
M
Cuzzocrea
Salvatore
S
Mazzon
Emanuela
E
Vacca
Carmine
C
Genovese
Tiziana
T
Migliorati
Graziella
G
Ayroldi
Emira
E
Riccardi
Carlo
C
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D003907:Dexamethasone / Q000008:administration & dosage; D050990:GATA3 Transcription Factor / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage; D051379:Mice; D008822:Mice, Transgenic; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D050800:STAT6 Transcription Factor / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D019076:Transgenes / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; C498608:Dsip1 protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007155:Immunologic Factors; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D014157:Transcription Factors; D001761:Bleomycin; D003907:Dexamethasone