Figures & data
Figure 1 Pleiotropic effects of IL-4 and IL-13 in asthma pathobiology. See text for details.
Note: Mainly produced by CD4+ Th2 cells and type 2 innate lymphoid cells (ILC2), IL-4, and IL-13 act on several cellular targets within the airways of asthmatic subjects. In particular, these two cytokines induce B lymphocytes to synthesize large amounts of immunoglobulin E (IgE) antibodies, and also promote the recruitment of eosinophils. Moreover, IL-13 elicits airway epithelial cell expression of iNOS, mucus production and goblet cell hyperplasia, stimulates ASM contraction and proliferation, and also enhances extracellular deposition of collagen and fibroblast to myofibroblast phenotypic transition. All these effects of IL-4 and IL-13 significantly contribute to airway inflammation and remodelling in asthma.
Abbreviations: ASM, airway smooth muscle; IL, interleukin; LTs, leukotrienes; iNOS, inducible nitric oxide synthase.
Abbreviations: ASM, airway smooth muscle; IL, interleukin; LTs, leukotrienes; iNOS, inducible nitric oxide synthase.
Figure 2 Membrane receptors and intracellular signaling pathways activated by IL-4 and/or IL-13. IL-4 and IL-13 exert their biological actions by activating a heterodimeric receptor complex consisting of the IL-4 receptor α-subunit (IL-4Rα) and the IL-13 receptor α1-subunit (IL-13Rα1).
Note: Binding of IL-13 to IL-13Rα1 induces heterodimerization with IL-4Rα. This dimerization, which can also be triggered by IL-4, activates JAK1/2 and Tyk2 tyrosine kinases, that are responsible for phosphorylation of STAT-6. Phosphorylated STAT-6 dimerizes and migrates from the cytosol to the nucleus, where it binds to the promoter regions of IL-4/IL-13-responsive genes. IL-13 can also bind to its receptor α2-chain (IL-13Rα2), which is not coupled to any dimerization mechanism or intracellular signaling pathway. The receptor/signaling complex constituted by IL-4Rα and γC chains, associated with JAK1/3 kinases, can be activated only by IL-4, but not by IL-13.
Abbreviations: IL, interleukin; JAK, Janus kinase; P, phosphorylation; STAT6, signal transducer and activator of transcription 6; Tik2, tyrosine kinase 2.
Abbreviations: IL, interleukin; JAK, Janus kinase; P, phosphorylation; STAT6, signal transducer and activator of transcription 6; Tik2, tyrosine kinase 2.
