Long-lived memory T-helper 17 (Th17) cells actively mediate the chronic inflammation in autoimmune disorders, including dry eye disease (DED). The mechanisms responsible for the maintenance and reactivation of these cells in autoimmunity have been subject of investigation. However, the process through which memory Th17 are generated from their effector precursors remains to be elucidated. Herein, using our murine model of DED, we detect a linear transition from effector-to-memory Th17 cells during the abatement phase of acute inflammation, which is accompanied by persistently high levels of IL-23 and diminished levels of IL-2. In addition, in vitro culture of effector Th17 cells derived from the DED animals with IL-23, but not IL-2, leads to significant generation of memory Th17 cells, along with upregulated expression levels of IL-7R and IL-15R by these cells. Furthermore, supplementation of IL-2 abolishes and blockade of IL-2 enhances IL-23-induced generation of memory Th17 cells in vitro. Finally, in vivo blockade of IL-23 signaling during the contraction phase of primary response inhibits the generation of memory Th17 cells from their effector precursors. Together, our data demonstrate a new dichotomy between IL-23 and IL-2 in driving effector Th17 cells into the memory pool in autoimmune-mediated ocular surface inflammation.

中文翻译：

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IL-23 和 IL-2 驱动自身免疫效应 T 辅助细胞 17 进入干眼病记忆池的功能。

长寿记忆 T 辅助细胞 17 (Th17) 细胞积极介导自身免疫性疾病的慢性炎症，包括干眼病 (DED)。在自身免疫中负责维持和重新激活这些细胞的机制已成为研究对象。然而，记忆 Th17 从其效应子前体产生的过程仍有待阐明。在此，使用我们的 DED 小鼠模型，我们检测到在急性炎症消退阶段从效应细胞到记忆 Th17 细胞的线性转变，伴随着持续高水平的 IL-23 和降低的 IL-2 水平。此外，来自具有 IL-23 而不是 IL-2 的 DED 动物的效应 Th17 细胞的体外培养导致记忆 Th17 细胞的显着产生，以及这些细胞上调的 IL-7R 和 IL-15R 表达水平。此外，IL-2 的补充消除和阻断 IL-2 增强了 IL-23 诱导的体外记忆 Th17 细胞的产生。最后，在初级反应的收缩阶段体内阻断 IL-23 信号传导会抑制记忆 Th17 细胞从其效应前体细胞中产生。总之，我们的数据证明了 IL-23 和 IL-2 在将效应 Th17 细胞驱动到自身免疫介导的眼表炎症的记忆池中的新二分法。在初级反应的收缩阶段体内阻断 IL-23 信号传导会抑制记忆 Th17 细胞从其效应前体细胞的产生。总之，我们的数据证明了 IL-23 和 IL-2 在将效应 Th17 细胞驱动到自身免疫介导的眼表炎症的记忆池中的新二分法。在初级反应的收缩阶段体内阻断 IL-23 信号传导会抑制记忆 Th17 细胞从其效应前体细胞的产生。总之，我们的数据证明了 IL-23 和 IL-2 在将效应 Th17 细胞驱动到自身免疫介导的眼表炎症的记忆池中的新二分法。