Basophil modulation by cytokine instruction.

Basophils have recently been recognized as critical effector cells in allergic reactions and protective immunity against helminths. Precise characterization of basophil biology could help to develop specific therapies that interfere with differentiation, tissue recruitment, or induction of effector functions and thereby ameliorate allergic disorders. The development, homeostasis, and effector functions of basophils are tightly regulated by extrinsic signals and in particular by cytokines. IL-3, GM-CSF, and thymic stromal lymphopoietin activate the STAT5 pathway that promotes proliferation, activation, and cytokine secretion but also induces a negative feedback loop via Pim-1 and SOCS proteins. Basophils further express receptors for IL-18 and IL-33, which are associated with the signaling adaptor MyD88 and activate the NF-κB and MAP kinase pathways. This review focuses on positive and negative regulation of basophils by these cytokines.