Interleukin 5 in the link between the innate and acquired immune response.

Interleukin-5 (IL-5) is an interdigitating homodimeric glycoprotein that is initially identified by its ability to support the in vitro growth and differentiation of mouse B cells and eosinophils. IL-5 transgenic mouse shows two predominant features, remarkable increase in B-1 cells resulting in enhanced serum antibody levels, predominantly IgM, IgA, and IgE classes and in expansion of eosinophil numbers in the blood and eosinophil infiltration into various tissues. Conversely, mice lacking a functional gene for IL-5 or IL-5 receptor alpha chain (IL-5Ralpha) display a number of developmental and functional impairments in B cells and eosinophils. IL-5 receptor (IL-5R) comprises alpha and betac chains. IL-5 specifically binds to IL-5Ralpha and induces the recruitment of betac to IL-5R. Although precise mechanisms on cell-lineage-specific IL-5Ralpha expression remain elusive, several transcription factors including Sp1, E12/E47, Oct-2, and c/EBPbeta have been shown to regulate its expression in B cells and eosinophils. JAK2 and JAK1 tyrosine kinase are constitutively associated with IL-5Ralpha and betac, respectively, and are activated by IL-5 stimulation. IL-5 activates at least three different signaling pathways including JAK2/STAT5 pathway, Btk pathway, and Ras/ERK pathway. IL-5 is one of key cytokines for mouse B cell differentiation in general, particularly for fate-determination of terminal B cell differentiation to antibody-secreting plasma cells. IL-5 critically regulates homeostatic proliferation and survival of and natural antibody production by B-1 cells, and enhances the AID and Blimp-1 expression in activated B-2 cells leading to induce mu to gamma1 class switch recombination and terminal differentiation to IgM- and IgG1-secreting plasma cells, respectively. In humans, major target cells of IL-5 are eosinophils. IL-5 appears to play important roles in pathogenesis of asthma, hypereosinophilic syndromes, and eosinophil-dependent inflammatory diseases. Clinical studies will provide a strong impetus for investigating the means of modulating IL-5 effects. We will discuss the role of IL-5 in the link between innate and acquired immune response, particularly emphasis of the molecular basis of IL-5-dependent B cell activation, allergen-induced chronic inflammation and hypereosinophilic syndromes on a novel target for therapy.