Nuocytes: expanding the innate cell repertoire in type-2 immunity

Activation and differentiation of the Th1 cell population lead to their production of the classical type-1 cytokines IFN-gamma, IL-2, and TNF-beta, thus promoting type-1 immunity. This is thought to occur via the ligation of TLRs by bacterial and viral products, which in turn, drive production of the essential Th1 cell differentiation factor, IL-12, by dendritic cells (DCs). Concurrent studies have been able to identify the effector cytokines produced by Th2 cells (IL-4, IL-5, IL-9, and IL-13) as being essential for parasitic immunity and also as essential factors in allergic asthma. However, the factors that are critical for initiation of the type-2 response remained obscure. Recently however, two critical observations have led to a more detailed understanding of the innate type-2 response. First, two novel, type-2-inducing cytokines-IL-25 and IL-33-were identified as being necessary for the up-regulation of the type-2 effector cytokines, mirroring the role of IL-12 in the type-1 response. Second, studies focused on target cell populations of IL-25 and IL-33 have identified novel, innate cell populations, which potentially bridge the gap between presentation of the type-2-inducing cytokine and the later adaptive Th2 cell response. In this review, we will discuss these new type-2 innate cell populations, in particular, the recently discovered nuocyte population, which are required for type-2 responses against helminthic parasites. J. Leukoc. Biol. 90: 867-874; 2011.