Deutsches Rheumaforschungszentrum Berlin, Berlin, Germany.
Eur J Immunol. 2010 Apr;40(4):1089-98. doi: 10.1002/eji.200939487.
Recently, IL-17 produced by Th17 cells was described as pro-inflammatory cytokine with an eminent role in autoimmune diseases, e.g. rheumatoid arthritis. A lack of IL-17 leads to amelioration of collagen-induced arthritis. IL-17 induction in naïve CD4(+) T cells depends on IL-6 and TGF-beta and is enhanced by IL-23. The in vivo inflammatory potential of in vitro-primed Th17 cells however, remains unclear. Here, we show that, although IL-17 neutralisation results in amelioration of murine OVA-induced arthritis, in vitro-primed Th17 cells cannot exacerbate arthritic symptoms after adoptive transfer. Furthermore, Th17 cells cannot induce an inflammatory delayed type hypersensitivity reaction because they fail to migrate into inflamed sites, possibly due to the lack of CXCR3 expression. Also, re-isolated Th17 cells acquired IFN-gamma expression, indicating instability of the Th17 phenotype. Taken together, the data show that IL-6, TGF-beta and IL-23 might not provide sufficient signals to induce "fully qualified" Th17 cells.
最近，Th17 细胞产生的白细胞介素-17（IL-17）被描述为一种促炎细胞因子，在自身免疫性疾病（如类风湿关节炎）中具有重要作用。缺乏 IL-17 可导致胶原诱导性关节炎的改善。幼稚 CD4+T 细胞中 IL-17 的诱导依赖于 IL-6 和 TGF-β，并受 IL-23 增强。然而，体外诱导的 Th17 细胞在体内的炎症潜力尚不清楚。在这里，我们表明，尽管 IL-17 中和可改善小鼠 OVA 诱导的关节炎，但体外诱导的 Th17 细胞在过继转移后不能加重关节炎症状。此外，Th17 细胞不能诱导炎症性迟发型超敏反应，因为它们不能迁移到炎症部位，可能是由于缺乏 CXCR3 表达。此外，重新分离的 Th17 细胞获得了 IFN-γ表达，表明 Th17 表型不稳定。综上所述，这些数据表明，IL-6、TGF-β 和 IL-23 可能不能提供足够的信号来诱导“完全合格”的 Th17 细胞。
