Therapeutic targeting of IL-17A and its receptor IL-17RA with antibodies has turned out to be a tremendous success in the treatment of several autoimmune conditions. As the IL-17 cytokine family consists of six members (IL-17A to F), it is intriguing to elucidate the biological function of these five other molecules to identify more potential targets. In the past decade, IL-17C has emerged as quite a unique member of this pro-inflammatory cytokine group. In contrast to the well-described IL-17A and IL-17F, IL-17C is upregulated at very early timepoints of several disease settings. Also, the cellular source of the homodimeric cytokine differs from the other members of the family: Epithelial rather than hematopoietic cells were identified as the producers of IL-17C, while its receptor IL-17RE is expressed on T_H17 cells as well as the epithelial cells themselves. Numerous investigations led to the current understanding that IL-17C (a) maintains an autocrine loop in the epithelium reinforcing innate immune barriers and (b) stimulates highly inflammatory T_H17 cells. Functionally, the IL-17C/RE axis has been described to be involved in the pathogenesis of several diseases ranging from infectious and autoimmune conditions to cancer development and progression. This body of evidence has paved the way for the first clinical trials attempting to neutralize IL-17C in patients. Here, we review the latest knowledge about identification, regulation, and function of the IL-17C/IL-17receptor E pathway in inflammation and immunity, with a focus on the mechanisms underlying tissue injury. We also discuss the rationale for the translation of these findings into new therapeutic approaches in patients with immune-mediated disease.

用抗体对IL-17A及其受体IL-17RA进行治疗靶向已证明在多种自身免疫性疾病的治疗中取得了巨大的成功。由于IL-17细胞因子家族由六个成员（IL-17A至F）组成，因此阐明这五个其他分子的生物学功能以鉴定更多潜在靶标非常有趣。在过去的十年中，IL-17C成为该促炎细胞因子组的独特成员。与众所周知的IL-17A和IL-17F相比，IL-17C在几种疾病的非常早的时间点上调。同样，同型二聚体细胞因子的细胞来源不同于该家族的其他成员：上皮细胞而非造血细胞被确定为IL-17C的产生者，而其受体IL-17RE在T _H上表达17个细胞以及上皮细胞本身。大量研究导致了目前的认识，即IL-17C（a）维持上皮的自分泌环，增强先天免疫屏障，（b）刺激高度炎症性T _H17个单元格。从功能上讲，IL-17C / RE轴被认为与几种疾病的发病机理有关，从传染性和自身免疫性疾病到癌症的发生和发展。这些证据为首次尝试中和患者的IL-17C铺平了道路。在这里，我们将综述有关炎症和免疫中IL-17C / IL-17受体E通路的鉴定，调控和功能的最新知识，重点是组织损伤的潜在机制。我们还讨论了将这些发现转化为免疫介导疾病患者的新治疗方法的基本原理。