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• IL-4 Signaling Pathways
• Other Common Cytokine Receptor Gamma-Chain Family Members
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Overview of IL-4 Signaling and its Primary Biological Effects in Different Immune Cell Types

Interleukin-4 (IL-4) is a glycosylated, type I cytokine with three intra-chain disulfide bridges that adopts a bundled four alpha-helix structure. It is primarily produced by T cells, natural killer T cells, mast cells, and eosinophils. IL-4 initiates signal transduction through one of two different receptor complexes, a type I receptor expressed on hematopoietic cells or a type II receptor expressed on nonhematopoietic cells. The type I receptor consists of the IL-4 R alpha and common gamma-chain/IL-2 R gamma subunits and is specific for IL-4, while the type II receptor consists of the IL-4 R alpha and IL-13 R alpha 1 subunits and can be activated by either IL-4 or IL-13. IL-4 signaling is required for the differentiation of Th2 and Th9 cells and regulates immunoglobulin class switching. In addition, IL-4 plays a central role in the development of allergic inflammation and asthma by enhancing the expression of Fc epsilon RI on B cells, mast cells, and basophils, promoting mast cell survival and proliferation, and inducing mast cell, basophil, and eosinophil chemotaxis.