CD1d-restricted iNKT cells are characterized by their expression of an invariant Vα14-Jα18 antigen receptor in mice and of an invariant Vα24-Jα18 in humans that recognizes glycolipid antigen presented by MHC class I-like molecule CD1d. Another distinguishing feature of iNKT cells is their promiscuous production of Th1, Th2, Th9 and Th17 cytokines. Here we identified iNKT cells consist from distinct functional subtypes based on the expression of IL-17 receptor B (IL-17RB), a receptor for IL-25: IL-17RB+ iNKT cells produce robust IL-13 and IL-9 with moderate IL-17A in response to IL-25, which is phenotypically and functionally distinct from classical IL-12-reactive IFN-γ-producing iNKT cells bearing CD122 without IL-17RB. In the in vivo experimental settings, IL-17RB+ iNKT cells play a crucial role in the induction of airway inflammation both of OVA and of RSV model. Through the elucidation of the mechanisms in the activation of IL-17RB+ iNKT cells, IL-18 instead of IL-25 is responsible for the activation of these cells in RSV model, resulting in an acute and robust production of Th2 and Th17 cytokines. Our findings reveal that IL-17RB+ iNKT cells and leading effector cells as target cells of IL-25 and IL-18 in the pathogenesis of airway diseases, illustrating the clinical potential of severe exacerbation of developing asthma by IL-17RB+ iNKT cell-dependent cellular cascade targeted therapy in humans.
- Copyright © 2013 by The American Association of Immunologists, Inc.