1. Enhanced Th2 cell differentiation and allergen-induced airway inflammation in Zfp35-deficient mice.
- Author
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Kitajima M, Iwamura C, Miki-Hosokawa T, Shinoda K, Endo Y, Watanabe Y, Shinnakasu R, Hosokawa H, Hashimoto K, Motohashi S, Koseki H, Ohara O, Yamashita M, and Nakayama T
- Subjects
- Administration, Inhalation, Adoptive Transfer, Allergens immunology, Animals, Asthma metabolism, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes transplantation, Carrier Proteins genetics, Cell Differentiation immunology, Cytokines immunology, Cytokines metabolism, Eosinophils metabolism, Inflammation immunology, Inflammation metabolism, Lung immunology, Lung pathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Ovalbumin immunology, Th2 Cells metabolism, Asthma immunology, CD4-Positive T-Lymphocytes immunology, Carrier Proteins metabolism, Eosinophils immunology, Th2 Cells immunology, Zinc Fingers
- Abstract
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.
- Published
- 2009
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