Repressor of GATA regulates TH2-driven allergic airway inflammation and airway hyperresponsiveness.
BACKGROUND
Studies of human asthma and of animal models of allergic inflammation/asthma highlight a crucial role for T(H)2 cells in the pathogenesis of allergic asthma. Repressor of GATA (ROG) is a POZ (BTB) domain-containing Kruppel-type zinc finger family (or POK family) repressor. A repressive function to GATA3, a master transcription factor for T(H)2 cell differentiation, is indicated.


OBJECTIVE
The aim of this study was to clarify the regulatory roles of ROG in the pathogenesis of T(H)2-driven allergic diseases, such as allergic asthma.


METHODS
We examined allergic airway inflammation and airway hyperresponsiveness (AHR) in 3 different mouse models, which use either ROG-deficient (ROG(-/-)) mice, ROG transgenic mice, or adoptive transfer of cells.


RESULTS
In ROG(-/-) mice T(H)2 cell differentiation, T(H)2 responses, eosinophilic airway inflammation, and AHR were enhanced. In ROG transgenic mice the levels of eosinophilic airway inflammation and AHR were dramatically reduced. Furthermore, adoptive transfer of T(H)2 cells with increased or decreased levels of ROG expression into the asthmatic mice resulted in reduced or enhanced airway inflammation, respectively.


CONCLUSIONS
These results indicate that ROG regulates allergic airway inflammation and AHR in a negative manner, and thus ROG might represent another potential therapeutic target for the treatment of asthmatic patients.
Hirahara
Kiyoshi
K
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Yamashita
Masakatsu
M
Iwamura
Chiaki
C
Shinoda
Kenta
K
Hasegawa
Akihiro
A
Yoshizawa
Hirohisa
H
Koseki
Haruhiko
H
Gejyo
Fumitake
F
Nakayama
Toshinori
T
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology; D050980:GATA Transcription Factors / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D012097:Repressor Proteins / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*
D050980:GATA Transcription Factors; D050990:GATA3 Transcription Factor; D012097:Repressor Proteins; C406863:Rog protein, mouse; D010047:Ovalbumin