白细胞介素-4 (IL-4) 是一种多效细胞因子，参与免疫应答的调节。IL-4 主要由肥大细胞、T 细胞、嗜酸性粒细胞和嗜碱性粒细胞分泌，是 IL-4 RA 的受体[1]。IL-4 的作用取决于其受体 IL-4 RA 招募的共享受体 γ 链 (γc) 类型。IL-2R γ 是多种白介素受体的共有亚基，(1) IL-4 RA 招募 IL-2R γ，与 IL-4 组成位于造血细胞上表达的 I 型信号复合物，导致一系列受体相关激酶介导的磷酸化事件。更重要的是，IL-2R γ 还参与了 IL-15 对中性粒细胞吞噬的刺激作用。并且，IL-4 受体复合物进一步导致细胞生长、抗凋亡、基因激活和分化的介质的募集。然而，(2) IL-4 RA 招募 IL-13RA1 链，会形成在非造血细胞上表达的 II 型复合物。其可能通过干扰 mTORC1 信号通路和诱导 RUFY4 来刺激树突状细胞的自噬。此外，IL-13RA1 在正常大脑的高级功能中起着至关重要的作用，如记忆和学习[2][3]。
具体来说，IL-4 参与调节抗原刺激的幼稚 T 细胞的分化，使其产生 IL-4 和其他细胞因子，包括 IL-5、IL-10 和 IL-13 等。同时，它也抑制 IFNγ 的产生细胞 CD4+ 的出现，延长培养条件下 T，B 淋巴细胞的寿命。其次，IL-4 还控制免疫球蛋白类转换，参与过敏性调节。它决定人的 B 细胞转向表达 IgE 和 IgG4，或是决定小鼠 B 细胞转向表达 IgE 和 IgG1。IL-4 还增加 B 细胞中 II 类 MHC 分子和 CD23 的表达，以参与免疫应答。IL-4 在组织粘附和炎症反应中也有重要作用。它与 TNF 共同作用，诱导血管内皮细胞粘附分子-1 (VCAM-11) 在血管内皮细胞上表达，并下调了选择素。IL-4 还发挥着蠕虫和其他细胞外寄生虫引起的保护性免疫作用[1]。
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].
