Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12
Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12
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DOI：
10.1016/s1074-7613(00)00070-4
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发表时间：
2000-11-01
期刊：
影响因子：
32.4
通讯作者：
Kastelein, RA
中科院分区：
文献类型：
--
作者：
Oppmann, B;Lesley, R;Kastelein, RA
在一次计算机筛选中发现的一个新序列似乎与白细胞介素 - 12的p35亚基有远亲关系。我们将这个因子称为p19，它自身没有生物活性；相反，它与白细胞介素 - 12的p40亚基结合形成一种新的、有生物活性的复合细胞因子，我们将其称为白细胞介素 - 23。活化的树突状细胞可分泌可检测水平的这种复合物。白细胞介素 - 23与白细胞介素 - 12受体β1结合，但不与白细胞介素 - 12受体β2结合；尽管如此，白细胞介素 - 23可激活植物血凝素刺激的T细胞中的信号转导子和转录激活子4（Stat4）。白细胞介素 - 23诱导小鼠记忆性（CD4⁺CD45Rb低表达）T细胞强烈增殖，这是白细胞介素 - 23的一种独特活性，因为白细胞介素 - 12对该细胞群没有影响。与人白细胞介素 - 12类似，人白细胞介素 - 23刺激植物血凝素刺激的T细胞以及CD45RO（记忆性）T细胞中干扰素 - γ的产生和增殖。
A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23. Activated dendritic cells secrete detectable levels of this complex. IL-23 binds to IL-12R beta1 but fails to engage IL-12R beta2; nonetheless, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low))T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory)T cells.