Department of Dermatology and Skin Science, Faculty of Medicine, Child and Family Research Institute, The University of British Columbia, Vancouver, British Columbia, Canada.
Department of Dermatology and Skin Science, Faculty of Medicine, Child and Family Research Institute, The University of British Columbia, Vancouver, British Columbia, Canada.
Clin Immunol. 2014 Sep;154(1):84-9. doi: 10.1016/j.clim.2014.06.006. Epub 2014 Jun 16.
Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing pancreatic beta cells. There is now mounting evidence that pro-inflammatory pathways, which are mediated by T cells that secrete IL-17 and IFN-γ, play a critical role in the loss of beta cells. These data suggest that blockade of T cells that secrete IL-17 and IFN-γ may halt or reverse disease in subjects with recent-onset T1D. Agents to facilitate this approach are currently in clinical use. Ustekinumab, a humanized monoclonal antibody that targets the shared p40 subunit of IL-12 and IL-23, has been used for the treatment of psoriasis, an indication for which it has proven to be safe and effective. In this review, we summarize the evidence that supports a combined pathogenic role of IL-17 and IFN-γ in the development of T1D, with the aim of providing a rationale for testing agents such as ustekinumab for the treatment of T1D.
1 型糖尿病（T1D）是由产生胰岛素的胰腺β细胞的自身免疫性破坏引起的。现在有越来越多的证据表明，由分泌 IL-17 和 IFN-γ 的 T 细胞介导的促炎途径在β细胞的丧失中起着关键作用。这些数据表明，阻断分泌 IL-17 和 IFN-γ 的 T 细胞可能阻止或逆转近期诊断为 T1D 的患者的疾病。目前有几种用于实现这一方法的药物正在临床使用。乌司奴单抗是一种针对 IL-12 和 IL-23 的共享 p40 亚单位的人源化单克隆抗体，已被用于治疗银屑病，其疗效和安全性已得到证实。在这篇综述中，我们总结了支持 IL-17 和 IFN-γ 在 T1D 发展中具有共同致病作用的证据，旨在为测试乌司奴单抗等药物治疗 T1D 提供依据。
