Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
J Invest Dermatol. 2013 Feb;133(2):479-88. doi: 10.1038/jid.2012.313. Epub 2012 Sep 6.
IL-27, a member of the IL-12 cytokine family, primes Th1 cell differentiation, whereas it suppresses Th17 cell development. We have previously reported that serum IL-27 levels are elevated in psoriatic patients and that IL-27 greatly induces in vitro production of Th1-type chemokines through STAT1 activation. In this study, to further investigate the in vivo role of IL-27 in the pathogenesis of psoriasis, we induced psoriasis-like inflammation on mouse back skin with topical application of imiquimod (IMQ), and continuously injected IL-27 or PBS subcutaneously. IMQ-treated skin showed an increase of IL-27 mRNA levels and the infiltration of IL-27-producing cells in the papillary dermis. The injection of IL-27 to the IMQ-treated skin exacerbated the disease compared with PBS injection. The IL-27 injection further augmented mRNA levels of IFN-γ, CXCL9, CXCL10, CXCL11, and TNF-α, without altering those of IL-17A, IL-17F, IL-22, and CCL20. Finally, IL-27 antagonism attenuated the upregulation of IFN-γ, CXCL9, CXCL10, CXCL11, and TNF-α mRNA levels, and induced clinical and histological improvement in the IMQ-treated skin. These results indicate that IL-27 would act in a proinflammatory manner, and thereby exacerbate the psoriasis-like skin inflammation induced by IMQ.
白细胞介素-27（IL-27）是白细胞介素-12 细胞因子家族的成员，它可诱导 Th1 细胞分化，同时抑制 Th17 细胞的发育。我们之前的研究表明，银屑病患者的血清白细胞介素-27（IL-27）水平升高，IL-27 通过 STAT1 激活，极大地诱导体外 Th1 型趋化因子的产生。在这项研究中，为了进一步研究白细胞介素-27（IL-27）在银屑病发病机制中的体内作用，我们通过咪喹莫特（IMQ）局部应用于小鼠背部皮肤诱导银屑病样炎症，并连续皮下注射白细胞介素-27（IL-27）或磷酸盐缓冲盐水（PBS）。IMQ 处理的皮肤中白细胞介素-27（IL-27）mRNA 水平增加，并且在乳头真皮中有白细胞介素-27（IL-27）产生细胞的浸润。与 PBS 注射相比，向 IMQ 处理的皮肤注射白细胞介素-27（IL-27）可加重疾病。白细胞介素-27（IL-27）注射进一步增加了 IFN-γ、CXCL9、CXCL10、CXCL11 和 TNF-α 的 mRNA 水平，而不改变 IL-17A、IL-17F、IL-22 和 CCL20 的水平。最后，白细胞介素-27（IL-27）拮抗剂可减弱 IFN-γ、CXCL9、CXCL10、CXCL11 和 TNF-α mRNA 水平的上调，并诱导 IMQ 处理的皮肤的临床和组织学改善。这些结果表明，白细胞介素-27（IL-27）可发挥促炎作用，并因此加重 IMQ 诱导的银屑病样皮肤炎症。
