ROG, repressor of GATA, regulates Th2-driven allergic airway inflammation and airway hyperresponsiveness (79.8)

Abstract

Abstract Studies of human asthma and of animal models of allergic inflammation/asthma highlight a crucial role for type 2 helper T (Th2) 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 Th2 cell differentiation is indicated. The aim of this study is to clarify the regulatory roles of ROG in the pathogenesis of Th2-driven allergic diseases, such as allergic asthma. We examined allergic airway inflammation and airway hyperresponsiveness in three different mouse models, which use either ROG-deficient (ROG-/-) mice, ROG transgenic mice or adoptive transfer of cells. In ROG-/- mice, Th2 cell differentiation, Th2 responses, eosinophilic airway inflammation and airway hyperresponsiveness were enhanced. In ROG transgenic mice, the levels of eosinophilic airway inflammation and airway hyperresponsiveness were dramatically reduced. Furthermore, adoptive transfer of Th2 cells with increased or decreased levels of ROG expression into the asthmatic mice resulted in reduced or enhanced airway inflammation, respectively. These results indicate that ROG regulates allergic airway inflammation and airway hyperresponsiveness in a negative manner, and thus ROG may represent another potential therapeutic target for the treatment of asthma patients.