Natural killer T-cells in asthma pathogenesis and treatment: old problems and future perspectives

Natural killer T-cells (NKT-cells) are immunological cells expressing features of both innate and adaptive immunity, which have been reported to be involved in the pathogenesis of asthma and in the induction of airway hyperresponsiveness (AHR). In this review we discuss the controversial results obtained in the past due to the lack of standardised analytical methods and the inhomogeneity of cohorts. In recent years, the availability of more advanced techniques led to a significant improvement in the phenotyping of these cells. Several research studies, both in mice and humans, reported that NKT-cells might be involved in the induction of AHR through the secretion of cytokines. In mouse models, in the absence of NKT-cells, AHR was not triggered and the airway eosinophil count was reduced. A relationship between NKT-cells and both innate (<i>e.g.</i> dendritic cells) and adaptive cells (<i>e.g.</i> Tregs) was demonstrated as well. These cells are seemingly able to produce different sets of cytokines, depending on their micro-environment. Moreover, numbers of NKT-cells derived from bronchoalveolar lavage were higher compared to those from peripheral blood samples. Lastly, the possibility to administer novel monoclonal antibodies against several interleukin (IL) pathways (such as anti-IL-5 and anti-IL-13, which can both be secreted by NKT-cells) further places these cells at the core of the pathogenesis of asthma and highlights the need for further discussion.