Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines
Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines
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DOI：
10.1182/blood-2005-05-2183
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发表时间：
2006-02-01
期刊：
影响因子：
20.3
通讯作者：
Riccardi, C
中科院分区：
文献类型：
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作者：
Cannarile, L;Fallarino, F;Riccardi, C
GILZ（glucocorticoid-induced leucine zipper）是地塞米松诱导的一个基因，参与T淋巴细胞活化和凋亡的调控。在本研究中，使用Gilz转基因小鼠（TG），过度表达GILZ的T细胞谱系，我们证明，Gilz是有牵连的辅助性T细胞-2（Th-2）反应的发展。经CD 3/CD 28抗体体外刺激后，TG小鼠外周血初始CD 4（+）T细胞分泌的Th-2细胞因子如白细胞介素-4（IL-4）、IL-5、IL-13和IL-10比野生型小鼠（WT）多，而产生的Th-1细胞因子如干扰素-γ（IFN-γ）比野生型小鼠（WT）少。在卵清蛋白（OVA）抗原免疫的特异性应答中，CD 4（+）TG淋巴细胞上调Th-2细胞因子表达。Th-2特异性转录因子加塔-3、信号转导子和转录激活子6（Stat 6）表达增加，Th-1分化相关转录因子T-bet表达减少。最后，在TG小鼠迟发型超敏反应，Th-1反应，被抑制和博莱霉素诱导的肺纤维化，Th-2介导的疾病，更严重。这些结果表明，Gilz有助于CD 4（+）向Th-2表型的承诺，并建议这种贡献可能是另一种机制占糖皮质激素免疫调节。
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 secretemore 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 glucocorticold immunomodulation.