Enhanced Th2 Cell Differentiation and Allergen-Induced Airway Inflammation in Zfp35-Deficient Mice

被引：9

作者：

Kitajima, Masayuki ^{[1
]}

Iwamura, Chiaki ^{[1
]}

Miki-Hosokawa, Takako ^{[1
]}

Shinoda, Kenta ^{[1
]}

Endo, Yusuke ^{[1
]}

Watanabe, Yukiko ^{[1
]}

Shinnakasu, Ryo ^{[1
]}

Hosokawa, Hiroyuki ^{[1
]}

Hashimoto, Kahoko ^{[2
,3
]}

Motohashi, Shinichiro ^{[1
]}

Koseki, Haruhiko ^{[4
]}

Ohara, Osamu ^{[5
]}

Yamashita, Masakatsu ^{[1
]}

Nakayama, Toshinori ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Immunol, Chuo Ku, Chiba 2608670, Japan

[2] Chiba Inst Technol, Dept Life & Environm Sci, Chiba, Japan

[3] Chiba Inst Technol, High Technol Res Ctr, Chiba, Japan

[4] RIKEN Res Ctr Allergy & Immunol, Lab Dev Genet, Yokohama, Kanagawa, Japan

[5] RIKEN Res Ctr Allergy & Immunol, Lab Immunogenom, Yokohama, Kanagawa, Japan

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 08期

关键词：

ZINC-FINGER PROTEIN; TRANSCRIPTION FACTOR GATA-3; T-HELPER-CELLS; HUMAN GENOME; LYMPHOCYTE-ACTIVATION; RECEPTOR EXPRESSION; LINEAGE COMMITMENT; GENE-EXPRESSION; ASTHMA; DISEASE;

D O I：

10.4049/jimmunol.0804155

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：5388 / 5396

页数：9