Innate Th2-type immune responses and the natural helper cell, a newly identified lymphocyte population

Abstract

We discuss recent progress in the understanding of Th2 cytokines derived from innate cells involved in the pathophysiology of various allergic diseases. Recent studies have identified a previously unrecognized lymphocyte population capable of producing Th2 cytokines in response to IL-25 and/or IL-33 independently of T or B cells. Newly identified cells responsive to IL-25 and/or IL-33 include natural helper cells, MPP, nuocytes and innate helper type 2 cells. These cells produce large amounts of Th2 cytokines, most notably IL-5 and IL-13, leading to eosinophilia and goblet cell hyperplasia and are critical for antihelminth reactions. IL-5 and IL-13 also play a role in pathophysiology of allergic diseases such as asthma and allergic diarrhea. There are similarities and differences between these newly identified cell populations. MPP cells can potentially differentiate to other myeloid cells, making this cell type distinct from the others. Natural helper cells constitutively produce Th2 cytokines, support the self-renewal of B1 cells and enhance IgA production. Unlike other innate Th2 producers, natural helper cells are present in fat-associated lymphoid clusters and likely play additional roles in the regulation of homeostasis in adipose tissues.