Interleukin (IL)-27 is a pleiotropic cytokine that initially was described as being pro-inflammatory and an inducer of T helper (Th)1 cells. In contrast, it has also been described as an anti-inflammatory cytokine in that it suppresses pro-inflammatory Th17 cells and induces anti-inflammatory IL-10 producing T regulatory (Tr)1 cells. While the majority of studies have been focused on the effects of IL-27 on T cells, human antigen-presenting cells express high levels of the IL-27 receptor ex vivo, in addition to being the major producer of IL-27. We report here that human monocytes are repressed by endogenous IL-27, in that the addition of an anti-IL-27 neutralizing antibody increases the production of pro-inflammatory cytokines ex vivo. We observed that neutralizing monocyte-derived IL-27 leads to increased IL-17A production by CD4+ T cells and a down-regulation of the IL-17 modulating ectonucleotidase CD39 on monocytes. The locus that contains the IL27 gene has been linked to susceptibility for type 1 diabetes (T1D). Interestingly, ex vivo monocytes from subjects with T1D produce more IL-27 suggesting this upregulation of IL-27 acts as a negative feedback loop to attempt to counterbalance the pro-inflammatory immune response in the disease state. In summary, we provide evidence that IL-27 is an endogenous regulator of human monocytes and has consequences on CD4+ T cell phenotype, particularly Th17 cells.

白细胞介素 (IL)-27 是一种多效性细胞因子，最初被描述为促炎剂和 T 辅助细胞 (Th)1 细胞的诱导剂。相比之下，它也被描述为一种抗炎细胞因子，因为它可以抑制促炎 Th17 细胞并诱导产生抗炎 IL-10 的调节性 T (Tr)1 细胞。虽然大多数研究都集中在 IL-27 对 T 细胞的影响，但人类抗原呈递细胞除了是 IL-27 的主要产生者之外，还离体表达高水平的 IL-27 受体。我们在此报道，人单核细胞受到内源性 IL-27 的抑制，因为添加抗 IL-27 中和抗体会增加离体促炎细胞因子的产生。我们观察到，中和单核细胞来源的 IL-27 会导致 CD4+ T 细胞产生 IL-17A 增加，并下调单核细胞上调节外切核苷酸酶 CD39 的 IL-17。含有IL27基因的基因座与 1 型糖尿病 (T1D) 的易感性有关。有趣的是，T1D 受试者的离体单核细胞产生更多的 IL-27，表明 IL-27 的上调充当负反馈环，试图平衡疾病状态下的促炎免疫反应。总之，我们提供的证据表明 IL-27 是人类单核细胞的内源性调节剂，并对 CD4+ T 细胞表型，特别是 Th17 细胞有影响。