Enhanced Th2 cell differentiation and allergen-induced airway inflammation in Zfp35-deficient mice.
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.
Kitajima
Masayuki
M
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Iwamura
Chiaki
C
Miki-Hosokawa
Takako
T
Shinoda
Kenta
K
Endo
Yusuke
Y
Watanabe
Yukiko
Y
Shinnakasu
Ryo
R
Hosokawa
Hiroyuki
H
Hashimoto
Kahoko
K
Motohashi
Shinichiro
S
Koseki
Haruhiko
H
Ohara
Osamu
O
Yamashita
Masakatsu
M
Nakayama
Toshinori
T
D000280:Administration, Inhalation; D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D016335:Zinc Fingers
D000485:Allergens; D002352:Carrier Proteins; D016207:Cytokines; C544687:Zfp35 protein, mouse; D010047:Ovalbumin