title: Lung dendritic cells undergo maturation and polarization towards a T helper type 2-stimulating phenotype in a mouse model of asthma: Role of nerve growth factor.
abstract: Nerve growth factor (NGF) and dendritic cells (DCs) have been hypothesized to modulate T cell responses in a mouse model of asthma. However, whether NGF plays a role in regulating the maturation and polarization of lung DCs remains unclear. In the present study, the effect of NGF inhibition on the maturation and phenotype of lung DCs was investigated in a mouse model of asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA), and subsequently received anti-NGF treatment. At 24 h following the last challenge, airway responsiveness and inflammation were examined. The concentrations of NGF, interferon (IFN)-γ and interleukin (IL)-4 were analyzed. In addition, maturation and CD103 expression in the lung DCs were investigated. Anti-NGF treatment was found to significantly reduce airway hyperreactivity and inflammation in asthmatic mice. In addition, a subdued T helper 2 (Th2) response was observed, characterized by the downregulation of IL-4 and the upregulation of IFN-γ. Furthermore, the expression of the DC surface molecules, CD80, CD86 and major histocompatibility complex class II, as well as the proportion of lung CD103+DCs, decreased in the OVA-sensitized and challenged mice. The proportion of lung CD103+DCs also exhibited a positive correlation with the levels of plasma NGF in the mice. These results may provide an explanation for the role of NGF in amplifying the Th2 response in allergic diseases. Therefore, NGF may promote the maturation and polarization towards a Th2-stimulating phenotype of activated DCs, contributing to an amplification of the Th2 response in asthma.
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Qingwu
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China ; Bronchial Asthma Research Center of Hunan Province, Changsha, Hunan 410008, P.R. China.
authors.forename: Pinhua
authors.initials: P
authors.lastname: Pan
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Zu
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China ; Bronchial Asthma Research Center of Hunan Province, Changsha, Hunan 410008, P.R. China.
authors.forename: Chengping
authors.initials: C
authors.lastname: Hu
keywords: asthma; lung dendritic cells; nerve growth factor