Aging is a significant risk factor for dry eye. Here we used a murine aging model to investigate the effects of aging on antigen presenting cells (APCs) and generation of pathogenic T helper (Th)-1 cells. Our results showed that APCs from aged mice accumulate at the conjunctiva, have higher levels of co-activation marker CD86 and lower aldehyde dehydrogenase activity. Using topical ovalbumin peptide as a surrogate antigen, we observed an increased number of antigen-loaded APCs in the draining cervical lymph nodes in the aged group and loss of tight junction protein occludin in the conjunctiva. Aged cervical lymph nodes APCs showed a greater generation of Th1 cells than young APCs in antigen-presentation assays in vitro. Aged lacrimal glands, and draining nodes showed an accumulation of IFN-γ producing CD4+T cells, while Th-17 cells were present only in aged draining nodes. There was also an age-related increase in CD4+CXCR3+IFN-γ+ cells in the conjunctiva, nodes, and lacrimal glands while CD4+CCR6+IL-17A+ cells increased in the draining nodes of aged mice. Adoptive transfer of aged CD4+CXCR3+ cells into young, naive immunodeficient recipients caused greater goblet cell loss than young CD4+CXCR3+ donor cells. Our results demonstrate that age-associated changes in APCs are critical for the pathogenesis of age-related dry eye.

中文翻译：

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年龄相关的抗原呈递细胞改变促进干眼诱导 Th1 细胞。

衰老是干眼症的重要危险因素。在这里，我们使用小鼠衰老模型来研究衰老对抗原呈递细胞 (APC) 和致病性 T 辅助细胞 (Th)-1 细胞生成的影响。我们的结果表明，来自老年小鼠的 APCs 在结膜处积聚，具有较高水平的共激活标记 CD86 和较低的醛脱氢酶活性。使用局部卵清蛋白肽作为替代抗原，我们观察到老年组颈部引流淋巴结中载有抗原的 APC 数量增加，结膜中紧密连接蛋白 occludin 丢失。在体外抗原呈递测定中，老年颈部淋巴结 APC 显示出比年轻 APC 更多的 Th1 细胞生成。老化的泪腺和引流淋巴结显示产生 IFN-γ 的 CD4+T 细胞聚集，而 Th-17 细胞仅存在于老化的引流节点中。结膜、淋巴结和泪腺中的 CD4+CXCR3+IFN-γ+ 细胞也随着年龄增长而增加，而老年小鼠的引流淋巴结中 CD4+CCR6+IL-17A+ 细胞增加。与年轻的 CD4+CXCR3+ 供体细胞相比，将衰老的 CD4+CXCR3+ 细胞过继转移到年轻、幼稚的免疫缺陷受体中会导致更大的杯状细胞损失。我们的结果表明，APC 的年龄相关变化对于年龄相关干眼症的发病机制至关重要。与年轻的 CD4+CXCR3+ 供体细胞相比，幼稚的免疫缺陷受体导致更大的杯状细胞损失。我们的结果表明，APC 的年龄相关变化对于年龄相关干眼症的发病机制至关重要。与年轻的 CD4+CXCR3+ 供体细胞相比，幼稚的免疫缺陷受体导致更大的杯状细胞损失。我们的结果表明，APC 的年龄相关变化对于年龄相关干眼症的发病机制至关重要。