Sulfatide-activated type II NKT cells prevent allergic airway inflammation by inhibiting type I NKT cell function in a mouse model of asthma

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 301; no. 6; pp. L975 - L984
• Main Authors: Zhang, Guqin, Nie, Hanxiang, Yang, Jiong, Ding, Xuhong, Huang, Yi, Yu, Hongying, Li, Ruyou, Yuan, Zhuqing, Hu, Suping
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.12.2011
• Subjects: Adoptive Transfer; Animals; Asthma; Asthma - chemically induced; Asthma - prevention & control; Bronchoalveolar Lavage Fluid; Cells; Cytokines; Female; Goblet Cells - drug effects; Goblet Cells - pathology; Hyperplasia - prevention & control; Immunoglobulin E - blood; Immunoglobulin G - blood; Interleukin-4 - metabolism; Interleukin-4 - secretion; Interleukin-5 - metabolism; Interleukin-5 - secretion; Lipids; Lung - drug effects; Lung - pathology; Mice; Mice, Inbred BALB C; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - metabolism; Natural Killer T-Cells - physiology; Natural Killer T-Cells - transplantation; Ovalbumin; Respiratory Mucosa - drug effects; Respiratory Mucosa - pathology; Rodents; Sulfoglycosphingolipids - pharmacology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00114.2011

Asthma is a common chronic inflammatory disease involving many different cell types. Recently, type I natural killer T (NKT) cells have been demonstrated to play a crucial role in the development of asthma. However, the roles of type II NKT cells in asthma have not been investigated before. Interestingly, type I and type II NKT cells have been shown to have opposing roles in antitumor immunity, antiparasite immunity, and autoimmunity. We hypothesized that sulfatide-activated type II NKT cells could prevent allergic airway inflammation by inhibiting type I NKT cell function in asthma. Strikingly, in our mouse model, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells result in reduced-inflammation cell infiltration in the lung and bronchoalveolar lavage fluid, decreased levels of IL-4 and IL-5 in the BALF; and decreased serum levels of ovalbumin-specific IgE and IgG1. Furthermore, it is found that the activation of sulfatide-reactive type II NKT cells leads to the functional inactivation of type I NKT cells, including the proliferation and cytokine secretion. Our data reveal that type II NKT cells activated by glycolipids, such as sulfatide, may serve as a novel approach to treat allergic diseases and other disorders characterized by inappropriate type I NKT cell activation.