Effect of NADPH oxidase 2 deficiency on allergic lung inflammation and differentiation of helper T cells (P6045)

Abstract

Abstract Nox2 has been originally identified in phagocytes, which kills engulfed pathogens by producing reactive oxygen species (ROS). It has been also revealed that activated T cells produce ROS that is an important second messenger for the functions of effector T cells. Recent studies have shown that Nox2 dificient CD4 T cells contain increased IL-17 producing capability and Nox2 knock-out mice have a tendency an enhanced susceptibility to spontaneous arthritis with age. To investigate whether Nox2 or ROS deficiency in T cells affect differentiation and function of CD4 T cells in T cell intrinsic manner. Specifically we adopted allergic asthma model to clarify the function of Th2 cells without Nox2 or ROS. Asthma phenotypes were analyzed in fungal protease mixed with chicken egg ovalbumin (OVA) allergen (APO) induced experimental asthma. To understand mechanisms of exaggerated effector T cell functions, we investigated the degree of T cell activation and differentiation of Treg cells with Nox2 deficient and wild type CD4 T cells. All experimental asthma phenotypes including airway hyper-responsiveness, lung inflammation along with eosinophilia and mucus production were increased in Nox2 deficient mice. Nox2 deficient T cells also showed enhanced hyper-activation, reduced AICD and decreased Treg cell differentiation. Our results indicate that Nox2/ROS deficiency showed exaggerated experimental asthma, which was caused by enhanced function of Th2 cells.