Il13 Il4

Production by TH2 cells TH1 cells Th0 cells

CD45RA* naive T cells CD45RO+ memory T cells Mast cells/basophils Effects on B cells Proliferation lgG4/lgE synthesis CD23 and HLA-DR expression Activation of immature B ceils Activation of pre-B cells Effects on T cells Proliferation Th2 cell differentiation Effects on monocytes CD23 and HLA-DR expression Synthesis of proinflammatory cytokines Synthesis of nitric oxide Effects on endothelial cells VCAM-1 expression

IL-4, IL-13 does not induce CD23, CD40 or HLA-DR expression or germline t RNA synthesis in CD19+, sp" human pre-B cells. These distinct effects of IL-4 and IL-13 on pre-B cells suggest that functional IL-13R is expressed at a later stage of B cell ontogeny than IL-4R and that IL-13, in contrast to IL-4, does not regulate early B cell maturation.

The different roles of IL-4 and IL-13 in the regulation of inflammatory responses in vivo are not only-determined because they act on partially different target cells but also because both cytokines can be produced by different cells. IL-13 is not only produced by T,,2 cells, but also by TH0 cells, and in contrast to IL-4 by naive CD45RA+ T cells and T,, 1 cells. However, all T cells that produce IL-4 produce IL-13 when studied at the single cell level. The kinetics of IL-13 production by activated T cells also differs significantly from that of IL-4. IL-4 mRNA appears 2-4 hours after activation, and it is almost undetectable after 12 hours, whereas IL-13 mRNA can still be observed 48 hours after T cell activation, suggesting that IL-13 is produced for significantly longer time periods after antigen-specific T cell activation.

There are also similarities in IL-4 and IL-13R signal transduction pathways. Both IL-4 and IL-13 induce phosphorylation of STAT6 (STAT = signal transducer and activator of transcription), which is also necessary for the biological activities of both cytokines. STAT6-deficient mice are unable to produce IgE and their T, ,2 cell differentiation is impaired. However IL-4, but not IL-13, induces phosphorylation of JAK3, which is probably due to the fact that JAK3 associates with the common y chain, which is not an essential component of IL-13R complex.

See also: Atopic allergy; CD40 and its ligand; Cytokines; IgE; Immunoglobulin class switching; Interleu-kin 4; Interleukin 4 receptor; T lymphocyte differentiation.

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