2013 Fiscal Year Final Research Report

Role of phospholipase Cepsilon in the respiratory immune system

Research Project

Project/Area Number	24790810
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Respiratory organ internal medicine
Research Institution	Kobe University
Principal Investigator	NAGANO Tatsuya 神戸大学, 医学(系)研究科(研究院), 研究員 (80624684)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	ホスホリパーゼCイプシロン / 喘息 / Th2細胞 / マウス / 卵白アルブミン
Research Abstract	Phospholipase Cepsilon (PLCepsilon) is an effector of Ras and Rap small GTPases and is highly expressed in non-immune cells such as epithelial cells. PLCepsilon has been shown to play a role in inflammation in the skin. This study aimed to elucidate its role in the respiratory immune system by employing an allergic asthma model using the mutant mice where PLCepsilon is enzymatically inactive. In the elicitation stage of the asthma, PLCepsilon deficient mice exhibited substantially attenuated airway hyper-responsiveness accompanied by reduced airway inflammation with a decrease in the Th2 cytokine levels. This attenuated airway inflammation seems to be caused by inhibition of cytokine production from the bronchial epithelial cells as demonstrated by immunohistochemical studies of the allergen-sensitized PLCepsilon deficient mice upon allergen challenge. These results demonstrate an important role of PLCepsilon in the respiratory immune system, at least that mediated by Th2 cells.