Development and function of invariant natural killer T cells producing T H2- and T H17-cytokines

There is heterogeneity in invariant natural killer t (inkt) cells based on the expression of cd4 and the il-17 receptor b (il-17rb),a receptor for il-25 which is a key factor in t h2 immunity. however,the development pathway and precise function of these inkt cell subtypes remain unknown. il-17rb + inkt cells are present in the thymic cd44 +/- nk1.1 - population and develop normally even in the absence of il-15,which is required for maturation and homeostasis of il-17rb - inkt cells producing ifn-γ. these results suggest that inkt cells contain at least two subtypes,il-17rb + and il-17rb - subsets. the il-17rb + inkt subtypes can be further divided into two subtypes on the basis of cd4 expression both in the thymus and in the periphery. cd4 + il-17rb + inkt cells produce t h2 (il-13),t h9 (il-9 and il-10),and t h17 (il-17a and il-22) cytokines in response to il-25 in an e4bp4-dependent fashion,whereas cd4 - il-17rb + inkt cells are a retinoic acid receptor-related orphan receptor (ror)γt + subset producing t h17 cytokines upon stimulation with il-23 in an e4bp4-independent fashion. these il-17rb + inkt cell subtypes are abundantly present in the lung in the steady state and mediate the pathogenesis in virus-induced airway hyperreactivity (ahr). in this study we demonstrated that the il-17rb + inkt cell subsets develop distinct from classical inkt cell developmental stages in the thymus and play important roles in the pathogenesis of airway diseases. © 2012 watarai et al.