The Effect of Activation of Invariant NKT Cells on the Allergic Airway Inflammation
Date Issued
2009
Date
2009
Author(s)
Wang, Tzu-Chun
Abstract
Asthma is an inflammatory lung disease characterized by the expansion of T helper 2 (Th2) cells and eosinophils as well as the production of allergen-specific IgE. Natural killer T (NKT) cell is a unique subset of T cells that coexpresses T cell receptor (TCR) and natural killer (NK) cell markers. The most studied NKT cells are Type 1 NKT cells, which also referred to invariant natural killer T cell (iNKT cells). iNKT cells express semi-invariant CD1d-restricted αβ TCR, therefore they can recognize glycolipid antigens (like α-galactosylceramide (α-GalCer)) presented by CD1d molecules on antigen presenting cells. Once NKT cells are activated, they rapidly produce large amount of cytokines, such as interferon-γ (IFN-γ) and interleukin-4 (IL-4). Due to this unique characteristic, they have been implicated in the regulation of immune responses associated with a broad range of diseases. In allergic asthma, the roles of iNKT cells are controversial. Some studies demonstrate that NKT cells are important in the development of asthma. However, others demonstrate that NKT cell activation before challenge abolishes the airway hyperresponsiveness and airway inflammation in experimental murine asthma models. These studies imply that NKT cells may play different roles in different asthma progression. Furthermore, this theory has been proved in some autoimmune diseases and allergic conjunctivitis. The aim of this study is to investigate the effect of activation of iNKT cells on the allergic airway inflammation and its mechanism. We administered BALB/c mice with α-GalCer, a stimulator for NKT cell activation, before or after ovalbumin (OVA) immunization and measured airway inflammation of those mice after 2 times of intranasal OVA challenge. In our results, the airway inflammation was more serious in mice that administered with α-GalCer before OVA immunization than that of after OVA immunization, suggesting that activation of iNKT cells in different asthma progression could lead to different severity of airway inflammation. Moreover, we analyzed the cell components and cytokines expression in lung after 2 hours and 5 days of α-GalCer administration to study the mechanism. Our data demonstrated that mice administered with α-GalCer before OVA immuniztion could activate iNKT cells to secrete large amount of Th2 cytokines, such as IL-4, IL-5 and IL-13, and increase eotaxin and thymic stromal lymphopoietin (TSLP) expression in bronchoalveolar lavage fluid (BALF), which recruit cell infiltrate in lung. In contrast, administration of α-GalCer after OVA immunization decreased Th2 cytokines, TSLP, and airway inflammation when compared to mice administered with a-GalCer before OVA immunization. Our data demonstrated that different immune response was noted in activation of naïve NKT cells and Th2-dominant environment NKT cells, which led to different outcome of airway inflammation in mice. However, the potential risks of treatment with NKT cell activation in human diseases should be considered.
Subjects
asthma
natural killer T cell (NKT cell)
airway inflammation
bronchoalveolar lavage fluid (BALF)
SDGs
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