Th17 cells in glaucoma patients promote Ig production in IL-17A and IL-21-dependent manner
Th17 cells in glaucoma patients promote Ig production in IL-17A and IL-21-dependent manner
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DOI：
10.1111/1440-1681.13141
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发表时间：
2019-10-01
影响因子：
2.9
通讯作者：
Su, Xingjie
中科院分区：
文献类型：
--
作者：
Ren, Yongbo;Qi, Yanxiu;Su, Xingjie
自身抗体表达升高是青光眼免疫失调的标志，可能导致视网膜神经节细胞凋亡和免疫介导的神经损伤，从而促进失明的发展。自身抗体上调的原因尚不清楚。Th17细胞可促进自身免疫和Ig的产生。在这里，我们证明血清白细胞介素(IL)-17A和IL-21水平在青光眼患者和非青光眼对照组之间是相似的。然而，青光眼患者th17促进细胞因子，如肿瘤坏死因子（TNF） IL-6的水平高于对照组。随后，我们证明青光眼患者体内Th17细胞水平上调，而这些细胞在体外直接处于静止状态。有趣的是，与非青光眼受试者的Th17细胞相比，青光眼患者的Th17细胞具有相似的IL-17A生产能力，但IL-21的生产能力明显更高。鉴于IL-21也被描述为滤泡辅助性T细胞的特异性细胞因子，研究了B细胞与循环Th17细胞共孵育后产生的Ig。青光眼患者的Th17细胞比对照组的Th17细胞具有显著增强的促进Ig生成的潜力。青光眼患者Th17细胞和对照Th17细胞都需要IL-17A和IL-21来产生Ig。总的来说，这项研究的结果表明青光眼患者的Th17细胞刺激Ig产生的能力升高。
Elevated expression of autoantibodies is a hallmark of immune dysregulation in glaucoma and may cause retinal ganglion cell apoptosis and immune-mediated nerve damage, thus contributing to the development of blindness. The cause of autoantibody upregulation remains unclear. Th17 cells are shown to promote autoimmunity and Ig production. Here, we demonstrate that the serum levels of interleukin (IL)-17A and IL-21 are comparable between glaucoma patients and non-glaucoma controls. However, the levels of Th17-promoting cytokines, such as tumour necrosis factor (TNF) IL-6, are higher in glaucoma patients than in controls. Subsequently, we demonstrate that glaucoma patients present upregulated levels of Th17 cells that are quiescent directly ex vivo. Interestingly, compared to the Th17 cells from non-glaucoma subjects, the Th17 cells from glaucoma patients present similar IL-17A production capacity but significantly higher IL-21 production capacity. Given that IL-21 is also described as a specific cytokine of follicular helper T cells, the Ig production by B cells following co-incubation with circulating Th17 cells is investigated. Th17 cells from glaucoma patients present significantly enhanced potential to promote Ig production than the Th17 cells from controls. Both glaucoma patient Th17 cells and control Th17 cells require IL-17A and IL-21 for Ig production. Overall, results from this study suggest that Th17 cells from glaucoma patients present elevated capacity to stimulate Ig production.