All roads lead to Rome: pathways of NKT cells promoting asthma.

NKT cells are the prominent manipulator in asthma development. Asthmatic NKT cells migrate from thymus, spleen, liver and bone marrow into blood vessels, and then concentrate in airway bronchi mucosa. This recruitment is dependent on high expression of CCR9 and engagement of CCL25/CCR9. NKT cells promote asthma in two different pathways. One is an indirect pathway. NKT cells contact with CD3(+) T cells and induce them secreting large quantity of Th2 cytokines (IL-4, IL-13), which requires the participation of dentritic cells and the synergic signaling of CCL25/CCR9 and CD226. The other is a direct pathway. Circulating asthmatic NKT cells selectively highly express Th1 cytokines (IFN-gamma). Once reached airway epithelium, most NKT cells shift to Th2-bias, highly expressing IL-4, IL-13, but not IFN-gamma. Both pathways lead to airway hyperresponsiveness and inflammation, asthma development. Comparing to the well documented suppressive regulatory T cells, CD4(+)CD25(+) T cells, NKT cells perform as a novel active regulator in asthma. These recent understanding of NKT cells performance in the development of asthma might unveil new therapy targets and management strategies for asthma.