白细胞介素-12 (IL-12)是白细胞介素-12亚单位α (IL12A, IL-12p35)和白细胞介素-12亚单位β (IL12B, IL-12p40)的异源二聚体。它是一种有效的免疫调节细胞因子,参与细胞内病原体介导免疫的产生。它由抗原呈递细胞产生,包括树突状细胞、巨噬细胞/单核细胞、中性粒细胞和一些B细胞(D’andrea et al. 1992, Kobayashi et al.1989, Heufler et al.1996)。它增强自然杀伤细胞(NK)和细胞毒性T细胞的细胞毒活性,刺激活化的NK细胞和T细胞的增殖,并诱导这些细胞产生干扰素γ (IFN γ) (Stern et al. 1990)。IL-12还通过诱导一类T辅助细胞(Th1)免疫反应促进细胞介导的免疫,在免疫调节中发挥重要作用。IL-12可能与类风湿关节炎等免疫病理条件有关(McIntyre et al. 1996)。IL-12受体是IL-12Rbeta1 (IL12RB1)和IL-12Rbeta2 (IL12RB2)的异源二聚体,两者都与白细胞介素-6受体亚基beta (IL6ST,gp130)高度同源。每个都有一个胞外配体结合结构域,一个跨膜结构域和一个胞质结构域,其中包含box 1和box 2序列,介导Janus家族酪氨酸激酶(JAKs)的结合。IL-12的结合被认为带来了异源二聚化和高亲和力受体复合物的产生,能够进行信号转导。在这个模型中,受体二聚导致胞质结构域并置,随后酪氨酸磷酸化和JAK2和TYK2的激活。 These activated kinases, in turn, tyrosine phosphorylate and activate several members of the signal transducer and activator of transcription (STAT) family, mainly STAT4, while also STAT1, STAT3 and STAT5 have been reported to be activated (Bacon et al. 1995, Jacobson et al. 1995, Yu et al. 1996, Gollob et al.1995). The STATs translocate to the nucleus to activate transcription of several genes, including IFN gamma. The production of IFN gamma has a pleiotropic effect in the cell, stimulating production of molecules important to cell mediated immunity. In particular, IFN gamma stimulates production of more IL-12 and sets up a positive regulation loop between IL-12 signaling and IFN gamma (Chan et al. 1991). The importance of IL-12 for this loop is demonstrated by IL-12 and STAT4 knockout mice that are severely compromised in IFN-gamma production (Kaplan et al. 1996; Magram et al. 1996), as well as by patients with IL12B mutations that are severely compromised in IFN-gamma production (Altare et al.1998).