IL-4

Interleukin-4 (IL-4) is a multipotent cytokine involved in the regulation of immune response. IL-4 is secreted mainly by mast cells, T cells, eosinophils and basophils, and is the receptor of IL-4 RA^[1]. The effect of IL-4 depends on the type of shared receptor gamma chain (γc) that its receptor IL-4 RA recruits. IL-2Rγ is a common subunit of several interleukin receptors. (1) IL-4 RA recruits IL-2Rγ and forms a Type I signaling complex with IL-4 expressed on hematopoietic cells, leading to a series of receptor-related kinase-mediated phosphorylation events. More importantly, IL-2Rγ is also involved in the stimulating effect of IL-15 on neutrophil phagocytosis. Moreover, the IL-4 receptor complex further leads to recruitment of mediators for cell growth, anti-apoptosis, gene activation, and differentiation. However, (2) IL-4 RA recruits the IL-13RA1 chain and forms a Type II complex expressed on non-hematopoietic cells. It may stimulate autophagy of dendritic cells by interfering with mTORC1 signaling pathway and inducing RUFY4. In addition, IL-13RA1 plays a vital role in higher functions of the normal brain, such as memory and learning^[2][3].
Specifically, IL-4 is involved in regulating the differentiation of antigen-stimulated naive T cells to produce IL-4 and other cytokines, including IL-5, IL-10, and IL-13. At the same time, it also inhibits the appearance of CD4+ of IFN-γ producing cells and prolongs the life of T and B lymphocytes under culture conditions. Secondly, IL-4 also controls immunoglobulin conversion and is involved in allergic regulation. It determines the conversion of human B cells to express IgE and IgG4, or mouse B cells to express IgE and IgG1. IL-4 also increases the expression of Class II MHC molecules and CD23 in B cells to participate in the immune response. IL-4 also plays an important role in tissue adhesion and inflammation. In conjunction with TNF, it induces the expression of vascular endothelial cell adhesion molecule-1 (VCAM-11) on vascular endothelial cells and down-regulates the selectin. IL-4 also plays a protective immune role induced by worms and other extracellular parasites^[1].

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