Cordoba-Rodriguez Ruth, Frucht David M
Laboratory of Cell Biology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Expert Opin Biol Ther. 2003 Aug;3(5):715-23. doi: 10.1517/14712598.3.5.715.
The recent discoveries of the two interleukin (IL)-12-related cytokines, IL-23 and IL-27, reveal that the regulation of cellular immunity is more complex than originally thought. Until these discoveries, the role of IL-12 in modulating cellular immune responses had been overestimated due to the belief that the IL-12 p40 subunit was unique to IL-12. However, because p40 is shared between IL-12 and IL-23, it would be expected that p40(-/-) mice are doubly deficient in IL-12 and IL-23. Indeed, the essential role previously attributed to IL-12 in experimental autoimmune encephalitis during studies of p40(-/-) mice has been shown to be due to IL-23 instead. The newest addition to the IL-12 cytokine family, IL-27, has unique features as well. Its specific action on naive CD4+ T cells in both mice and humans appears to distinguish it from the other IL-12 family members. Although related, the IL-12 family of cytokines and their receptors have distinct patterns of expression and unique effects on developing immune responses. This review summarises much of the pertinent literature on the IL-12 cytokine family and provides predictions regarding their potential therapeutic roles based on what has been learned about their functions in vitro and in vivo in gene-deficient mice.
最近发现的两种白细胞介素（IL）-12相关细胞因子，即IL-23和IL-27，揭示了细胞免疫的调节比原先认为的更为复杂。在这些发现之前，由于认为IL-12 p40亚基是IL-12所特有的，IL-12在调节细胞免疫反应中的作用被高估了。然而，由于p40在IL-12和IL-23之间是共享的，可以预期p40（-/-）小鼠在IL-12和IL-23方面都是双重缺陷的。事实上，在对p40（-/-）小鼠的研究中，先前归因于IL-12在实验性自身免疫性脑脊髓炎中的关键作用已被证明是由IL-23所致。IL-12细胞因子家族的最新成员IL-27也有其独特之处。它对小鼠和人类的初始CD4 + T细胞的特异性作用似乎使其有别于其他IL-12家族成员。虽然相关，但细胞因子IL-12家族及其受体具有不同的表达模式，并且对免疫反应的发育具有独特的影响。这篇综述总结了许多关于IL-12细胞因子家族的相关文献，并根据在基因缺陷小鼠的体内和体外功能研究中所了解到的情况，对它们的潜在治疗作用进行了预测。
