Invariant NKT Cells Act as an Adjuvant to Enhance Th2 Inflammatory Response in an OVA-Induced Mouse Model of Asthma

Hanxiang Nie,Guqin Zhang,Suping Hu,Qing He,Min Liu,Qiaoyu Yang,Ping Li,Hongying Yu,Xuhong Ding,Yi Huang,Ailing Wang,Jiong Yang,Gobardhan Das

doi:10.1371/journal.pone.0119901

Abstract

BackgroundInvariant natural killer T cells (iNKT cells) are a unique subset of T lymphocytes and are considered to play an important role in the development of allergic bronchial asthma. Recently, iNKT cells were shown to play an immunoregulatory role in CD4+ and CD8+ T cell-mediated adaptive immune response. Allergen-specific Th2 inflammatory responses are an important part of the adaptive immune response in asthma. However, the regulatory functions of the Th2 inflammatory response in asthma have not been studied in detail.MethodIn this study, we have investigated the regulatory functions of iNKT cells on the Th2 inflammatory response in an ovalbumin (OVA)-induced murine model of asthma.ResultsOur results demonstrate that α-Galactosylceramide (α-GalCer) administration activated iNKT cells but could not induce the Th2 inflammatory response in wild-type (WT) mice. In the OVA-induced asthma model, α-GalCer administration and adoptive transfer of iNKT cells significantly augmented the Th2 inflammatory responses, including elevated inflammatory cell infiltration in the lung and bronchoalveolar lavage fluid (BALF); increased levels of IL-4, IL-5, and IL-13 in the BALF and splenocyte culture supernatant; and increased serum levels of OVA-specific IgE and IgG1. In addition, the Th2 inflammatory response was reduced, but not completely abrogated in CD1d-/- mice immunized and challenged with OVA, compared with WT mice.ConclusionThese results suggest that iNKT cells may serve as an adjuvant to enhance Th2 inflammatory response in an OVA-induced murine model of asthma.

Highlights

Asthma, a complex inflammatory disease of the airways, is traditionally driven by allergenspecific IgE and T helper (Th) 2 cells [1]
Our results demonstrate that α-Galactosylceramide (α-GalCer) administration activated iNKT cells but could not induce the Th2 inflammatory response in wild-type (WT) mice
The Th2 inflammatory response was reduced, but not completely abrogated in CD1d-/- mice immunized and challenged with OVA, compared with WT mice. These results suggest that iNKT cells may serve as an adjuvant to enhance Th2 inflammatory response in an OVA-induced murine model of asthma

Summary

Introduction

A complex inflammatory disease of the airways, is traditionally driven by allergenspecific IgE and T helper (Th) 2 cells [1]. The allergen-specific Th2 cells orchestrate the inflammation process in asthma by producing Th2 cytokines, such as IL-4, IL-5, and IL-13, which enhance allergen-specific IgE synthesis, increase airway mucus production and the growth and differentiation of airway eosinophils, and directly induce the development of airway hyperresponsiveness (AHR), a cardinal feature of asthma [1] This notion was challenged when the role for invariant natural killer T cells (iNKT cells) in the development of asthma was identified [2]. Allergen-specific Th2 inflammatory responses are an important part of the adaptive immune response in asthma [14] and our previous study showed that allergic airway inflammation was reduced but not completely abrogated when the activity of iNKT cells was inhibited in a mouse model of asthma [15]. The regulatory functions of the Th2 inflammatory response in asthma have not been studied in detail

Methods

Results

Conclusion