Interleukin-13 (IL-13) is a monomeric 17 kDa immunoregulatory cytokine that plays a key role in the pathogenesis of allergy, cancer, and tissue fibrosis. It is secreted by several helper T cell subsets, NK cells, mast cells, eosinophils, basophils, and visceral smooth muscle cells [1-3]. Mature human IL-13 shares approximately 58% amino acid sequence identity with mouse and rat IL-13. Despite the low homology, it exhibits cross-species activity between human, mouse, and rat [4]. IL-13 suppresses the production of proinflammatory cytokines and other cytotoxic substances by macrophages, fibroblasts, and endothelial cells. On B cells, it promotes cellular activation, immunoglobulin class switching to IgE, and the up-regulation of CD23/Fc epsilon RII [1, 5]. IL-13 binds with low affinity to the transmembrane IL-13 R alpha 1 which then forms a signaling complex with the transmembrane IL-4 R alpha [6-8]. This high affinity receptor complex also functions as the type 2 IL-4 receptor [6, 7]. IL-13 R alpha 2 inhibits responses to both IL-13 and IL-4. It binds IL-13 with high affinity [9, 10] and prevents IL-13 from signaling through the IL-13 R alpha 1/IL-4 R alpha complex [11, 12]. It also blocks signaling through IL-4-occupied IL-13 R alpha 1/IL-4 R alpha receptor complexes [12, 13]. In addition, IL-13-bound IL-13 R alpha 2 can directly promote tumor cell invasiveness and the development of tissue fibrosis [14-16].
Reference
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