Innate immune cell populations function as initiators and effectors in Th2 cytokine responses.

The recent identification of previously unrecognized innate cell populations, termed natural helper cells (NHCs), multi-potent progenitor type 2 (MPP(type2)) cells, nuocytes, and innate type 2 helper (Ih2) cells has provided new insights into our understanding of the cellular mechanisms that lead to the development of CD4(+) Th2 cell-dependent immunity and/or inflammation at mucosal sites. In this review, we focus on the functional significance, similarities, and differences between NHCs, MPP(type2) cells, nuocytes and Ih2 cells. All four cell populations are activated by interleukin (IL)-25 and/or IL-33 and are capable of promoting Th2 cytokine responses. Collectively, the identification of these cell populations might illuminate ancient evolutionary conserved pathways that are involved in the development of Th2 cytokine responses, and could be of benefit in the development of therapeutic approaches that target helminth infections and allergic diseases.