Antigen-Specific IgG ameliorates allergic airway inflammation via Fcγ receptor IIB on dendritic cells

Yumiko Ishikawa,Yoshihiro Nishimura,Hajime Karasuyama,Kazuyuki Kobayashi,Tetsuya Takagawa,Yasuhiro Funada,Yoshikazu Kotani,Masatsugu Yamamoto,Kyosuke Nakata,Masaru Yoshida

doi:10.1186/1465-9921-12-42

Yumiko Ishikawa, Yoshihiro Nishimura + Show 8 more

Open Access

https://doi.org/10.1186/1465-9921-12-42

Copy DOI

Abstract

BackgroundThere have been few reports on the role of Fc receptors (FcRs) and immunoglobulin G (IgG) in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs) in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa.MethodsIn FcγRIIB deficient (KO) and C57BL/6 (WT) mice, the effects of intratracheal instillation of antigen-specific IgG were analysed using the model with sensitization and airborne challenge with ovalbumin (OVA). Thoracic lymph nodes instilled with fluorescein-conjugated OVA were analysed by fluorescence microscopy. Moreover, we analysed the CD11c+ MHC class II+ cells which intaken fluorescein-conjugated OVA in thoracic lymph nodes by flow cytometry. Also, lung-derived CD11c+ APCs were analysed by flow cytometry. Effects of anti-OVA IgG1 on bone marrow dendritic cells (BMDCs) in vitro were also analysed. Moreover, in FcγRIIB KO mice intravenously transplanted dendritic cells (DCs) differentiated from BMDCs of WT mice, the effects of intratracheal instillation of anti-OVA IgG were evaluated by bronchoalveolar lavage (BAL).ResultsIn WT mice, total cells and eosinophils in BAL fluid reduced after instillation with anti-OVA IgG1. Anti-OVA IgG1 suppressed airway inflammation in hyperresponsiveness and histology. In addition, the number of the fluorescein-conjugated OVA in CD11c+ MHC class II+ cells of thoracic lymph nodes with anti-OVA IgG1 instillation decreased compared with PBS. Also, MHC class II expression on lung-derived CD11c+ APCs with anti-OVA IgG1 instillation reduced. Moreover, in vitro, we showed that BMDCs with anti-OVA IgG1 significantly decreased the T cell proliferation. Finally, we demonstrated that the lacking effects of anti-OVA IgG1 on airway inflammation on FcγRIIB KO mice were restored with WT-derived BMDCs transplanted intravenously.ConclusionAntigen-specific IgG ameliorates allergic airway inflammation via FcγRIIB on DCs.

Highlights

There have been few reports on the role of Fc receptors (FcRs) and immunoglobulin G (IgG) in asthma
Intratracheal instillation of anti-OVA IgG1 ameliorated T helper 2 (Th2) response allergic airway inflammation to a greater degree than anti-OVA IgG 2a In WT mice, anti-OVA IgG subclass instillation significantly decreased the number of total cells and eosinophils in bronchoalveolar lavage (BAL) fluid as compared with phosphate-buffered saline (PBS) group, nonspecific IgG did not decrease (Figure 1A)
IL-4, IL-5, and IL-13 in BAL fluid of anti-OVA IgG1 instillation significantly decreased compared with PBS group, on the other hand, anti-OVA IgG1 instillation increased IFN-g cytokine levels in BAL fluid compared with PBS (Figure 1B)

Summary

Introduction

There have been few reports on the role of Fc receptors (FcRs) and immunoglobulin G (IgG) in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs) in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa. The. Bronchial asthma is characterized by allergic inflammation of the bronchial mucosa, in addition to airway hyperresponsiveness (AHR), and elevated titers of circulating IgE. Antigen-specific IgE binds to FcεRI on mast cells and FcεRII on eosinophils and macrophages [2]. As a result of IgE cross-linking after antigen inhalation, an immediate allergic reaction is induced. When the inhaled allergen is recognized and presented by antigen presenting cells (APCs) in the airway, T cells are activated and differentiate from Th0 cells into Th2-type cells.

Objectives

Methods

Results

Conclusion