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.

Qingwu Qin,Chengping Hu,Zhan Wang,Pinhua Pan,Qing Xia,Zu Cao,Hongyi Tan

doi:10.3892/etm.2014.1967

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.

Highlights

Allergic asthma affects 1-18% of the population in different countries and represents one of the most common diseases [1]
Expression levels of nerve growth factor (NGF) were analyzed in the lung tissues and serum to determine whether NGF production increased in asthmatic mice
Treatment with control immunoglobulin G (IgG) did not exhibit a marked effect on methacholine‐induced hyperreactivity, with the RL in the control IgG‐treated mice not significantly different when compared with the asthmatic mice

Summary

Introduction

Allergic asthma affects 1-18% of the population in different countries and represents one of the most common diseases [1]. Asthma is a chronic inflammatory airway disease characterized by recurrent episodes of wheezing, breathlessness, chest tightness and coughing driven by an aberrant T helper 2 (Th2) immune response to environmental allergens [2]. In addition to its classical nervous system domain, nerve growth factor (NGF) is regarded as an important factor involved in the pathogenesis of allergic diseases, including asthma [3]. Studies in ovalbumin sensitized and challenged asthmatic mice with anti-NGF antibody [4] or small interfering RNA [5] have shown that blocking NGF can improve airway inflammation. Transgenic mice overexpressed NGF in the airways had more severe airway inflammation compared with wild-type mice when ovalbumin sensitized and challenged [4]. The mechanisms underlying the effects of NGF on inflammation in asthma remain unclear

Methods

Results

Conclusion