Enhanced Th2 Cell Differentiation and Allergen-Induced Airway Inflammation in Zfp35-Deficient Mice
Enhanced Th2 Cell Differentiation and Allergen-Induced Airway Inflammation in Zfp35-Deficient Mice
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DOI：
10.4049/jimmunol.0804155
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发表时间：
2009-10-15
影响因子：
4.4
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
--
作者：
Kitajima, Masayuki;Iwamura, Chiaki;Nakayama, Toshinori
人类哮喘和变应性气道炎症动物模型的研究揭示了Th2细胞在变应性哮喘发病机制中的重要作用。kruppel型锌指蛋白是细胞发育和功能调控转录因子中最大的家族。锌指蛋白（Zfp） 35是一种含有18锌指基序的kruppel型锌指蛋白，其功能尚不清楚。本研究的目的是阐明Zfp35在th2依赖性变应性炎症（如过敏性哮喘）发病机制中的作用。我们在两种小鼠模型中检测了气道嗜酸性粒细胞炎症和高反应性，这两种小鼠模型使用我们新生成的Zfp35缺陷（Zfp35(-/-)）小鼠和过继细胞转移。在Zfp35（-/-）小鼠中，Th2细胞分化、Th2细胞因子产生、嗜酸性炎症和气道高反应性显著增强。此外，将ag致敏的Zfp35(-/-) CD4 T细胞过继转移到哮喘小鼠体内，导致气道炎症和气道高反应性增强。这些结果表明Zfp35以阴性方式控制Th2细胞分化，过敏性气道炎症和气道高反应性。因此，Zfp35可能控制th2依赖性疾病，如过敏性哮喘。中华免疫学杂志，2009,18(3):588 - 596。
Studies of human asthma and of animal models of allergic airway inflammation revealed a crucial role for Th2 cells in the pathogenesis of allergic asthma. Kruppel-type zinc finger proteins are the largest family of a regulatory transcription factor for cellular development and function. Zinc finger protein (Zfp) 35 is an 18-zinc finger motif-containing Kruppel-type zinc finger protein, while its function remains largely unknown. The aim of this study was to clarify the role of Zfp35 in the pathogenesis of Th2-dependent allergic inflammation, such as allergic asthma. We examined airway eosinophilic inflammation and hyperresponsiveness in two mouse models, which use our newly generated Zfp35-deficient (Zfp35(-/-)) mice and adoptive transfer of cells. In Zfp35(-/-) mice, Th2 cell differentiation, Th2 cytokine production, eosinophilic inflammation, and airway hyperresponsiveness were substantially enhanced. Furthermore, adoptive transfer of Ag-sensitized Zfp35(-/-) CD4 T cells into the asthmatic mice resulted in enhanced airway inflammation and airway hyperresponsiveness. These results indicate that Zfp35 controls Th2 cell differentiation, allergic airway inflammation, and airway hyperresponsiveness in a negative manner. Thus, Zfp35 may control Th2-dependent diseases, such as allergic asthma. The Journal of Immunology, 2009, 183: 5388-5396.