Possible roles of IL-27 in the imiquimod-induced psoriasis like skin inflammation

IL-27 在咪喹莫特诱导的银屑病样皮肤炎症中的可能作用

• 批准号: 23890043
• 负责人: SHIBATA Sayaka
• 金额: $ 2.08万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23890043/
• 关键词: 乾癬; 皮膚免疫・炎症学; IL-27; イミキモド

IL-27, a member of IL-12 cytokine family, primes Th1 cell differentiation, while 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 pathogensis of psoriasis, we induced psoriasis-like inflammation on mouse back skin with topical application of imiquimod, and continuously injected IL-27 or PBS subcutaneously. Imiquimod-treated skin showed the 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 imiquimod-treated skin exacerbated the disease compared with PBS injection. The IL-27 injection further augmented mRNA levels of IFN-〓, CXCL9, CXCL10, CXCL11, and TNF-〓, without altering those of IL-17A, IL-17F, IL-22, and CCL20. Finally, IL-27 antagonism attenuated the upregulation of IFN-〓, CXCL9, CXCL10, CXCL11 and TNF-〓 mRNA levels, and induced clinical and histological improvement in the imiquimod-treated skin. These results indicate that IL-27 would act in aproinflammatory manner, and thereby exacerbates the psoriasis-like skin inflammation induced by imiquimod.

IL-27是IL-12细胞因子家族的一员，它启动Th 1细胞分化，同时抑制Th 17细胞发育。我们以前曾报道，银屑病患者血清IL-27水平升高，IL-27通过STAT 1激活极大地诱导体外产生Th 1型趋化因子。在这项研究中，为了进一步研究IL-27在银屑病发病机制中的体内作用，我们通过局部应用咪喹莫特在小鼠背部皮肤上诱导银屑病样炎症，并连续皮下注射IL-27或PBS。咪喹莫特处理的皮肤显示IL-27 mRNA水平的增加和IL-27产生细胞在乳头状真皮中的浸润。与PBS注射相比，将IL-27注射到咪喹莫特处理的皮肤加重了疾病。IL-27注射进一步增加了IFN-γ、CXCL 9、CXCL 10、CXCL 11和TNF-α的mRNA水平，而不改变IL-17 A、IL-17 F、IL-22和CCL 20的mRNA水平。最后，IL-27拮抗作用减弱了IFN-γ、CXCL 9、CXCL 10、CXCL 11和TNF-α mRNA水平的上调，并诱导咪喹莫特处理的皮肤的临床和组织学改善。这些结果表明IL-27将以抗炎方式起作用，从而加剧由咪喹莫特诱导的银屑病样皮肤炎症。

项目成果

IL-27 activates Th1-mediated responses in imiquimod-induced psoriasis-like skin lesions.

• DOI: 10.1038/jid.2012.313
• 发表时间: 2013-02
• 期刊: The Journal of investigative dermatology
• 作者: S. Shibata;Y. Tada;Y. Asano;K. Yanaba;M. Sugaya;T. Kadono;N. Kanda;Shinichi Watanabe;S. Sato-S.-Sat