The functions of IL-23 and IL-2 on driving autoimmune effector T-helper 17 cells into the memory pool in dry eye disease.
The functions of IL-23 and IL-2 on driving autoimmune effector T-helper 17 cells into the memory pool in dry eye disease.
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DOI：
10.1038/s41385-020-0289-3
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发表时间：
2021-01
影响因子：
8
通讯作者：
Dana R
中科院分区：
文献类型：
--
作者：
Chen Y;Shao C;Fan NW;Nakao T;Amouzegar A;Chauhan SK;Dana R
长寿命记忆Th17细胞积极参与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一直是研究的对象。然而，记忆Th17是通过其效应器前体产生的过程仍有待阐明。在这里，使用我们的DED小鼠模型，我们检测到在急性炎症缓解阶段从效应细胞到记忆性Th17细胞的线性转变，伴随着持续高水平的IL-23和低水平的IL-2。此外，体外培养来自DED动物的效应Th17细胞与IL-23，而不是IL-2，导致显著的记忆Th17细胞的产生，以及这些细胞上调IL-7R和IL-15R的表达。此外，补充IL-2可取消，阻断IL-2可增强IL-23诱导的Th17记忆细胞的体外生成。最后，在体内，在初级反应的收缩阶段阻断IL-23信号会抑制记忆Th17细胞从其效应器前体产生。总之，我们的数据表明，在自身免疫介导的眼表炎症中，IL-23和IL-2在驱动效应Th17细胞进入记忆池方面存在新的二分法。
Long-lived memory 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. Additionally, 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 up-regulated expressions 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.
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白介素-7和-15在自身免疫中维持致病记忆Th17细胞。
影响因子：
12.8
作者：
Chen Y;Chauhan SK;Tan X;Dana R
通讯作者：
Dana R
DOI：
10.1084/jem.20062381
发表时间：
2007-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dooms H;Wolslegel K;Lin P;Abbas AK
通讯作者：
Abbas AK
DOI：
10.1084/jem.20071855
发表时间：
2008-01-21
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Löhning M;Hegazy AN;Pinschewer DD;Busse D;Lang KS;Höfer T;Radbruch A;Zinkernagel RM;Hengartner H
通讯作者：
Hengartner H
影响因子：
4.4
作者：
Cunin, Pierre;Caillon, Antoine;Jeannin, Pascale
通讯作者：
Jeannin, Pascale
影响因子：
30.5
作者：
通讯作者：
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