Regulation of cytokine expression by human blood basophils

IL-4 and IL-13 are key immunoregulatory cytokines because of their ability to induce and amplify Th2-type immune responses and by promoting IgE formation. The basophil is a particularly prominent source of IL-4/IL-13, which are rapidly produced upon Fc epsilonRI cross-linking. Cytokine expression by basophils is unique and distinct from other cell types, since: (1) Basophils are the only cell type constitutively expressing IL-4 and IL-13 mRNA. IL-4/IL-13 message and protein are expressed in a very restricted manner, since neither the mRNAs nor the protein products of most proinflammatory Th1-type, and even Th2-type, cytokines or chemokines are expressed; (2) Basophils secrete IL-4/IL-13 also upon IgE-independent activation (IL-3 plus C5a), and they are thereby potentially capable of initiating a Th2 response. Furthermore, we identified an adjuvant from helminths capable of directly inducing IL-4 formation, and (3) IL-4 expression by basophils is resistant to counter-regulatory effectors inhibiting Th2 development. Studies about the regulation of IgE-dependent and -independent IL-4/IL-13 expression by different cytokines, growth factors and chemokines demonstrate that the different basophil effector functions such as chemotaxis, exocytosis, leukotriene C4 formation and cytokine expression are regulated separately. Thus, our study supports a key immunoregulatory role of basophils in the skewing of immune responses to Th2.