Natural killer T cells and the regulation of asthma

A crucial role has been suggested for invariant natural killer T cells (iNKT) in regulating the development of asthma, a complex and heterogeneous disease characterized by airway inflammation and airway hyperreactivity (AHR). iNKT cells constitute a unique subset of T cells responding to endogenous and exogenous lipid antigens, rapidly secreting a large amount of cytokines, which amplify both innate and adaptive immunity. Herein, we review recent studies showing a requirement for iNKT cells in various models of asthma in mice and monkeys as well as studies in human patients. Surprisingly, in several different murine models of asthma, distinct subsets of iNKT cells were required, suggesting that iNKT cells serve as a common critical pathogenic element for many different forms of asthma. The importance of iNKT cells in both allergic and non-allergic forms of asthma, which are independent of adaptive immunity and associated with airway neutrophils, may explain situations previously found to be incompatible with the Th2 paradigm of asthma.