Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul 03080, Korea.
Department of Ophthalmology, Seoul National University College of Medicine, Seoul 03080, Korea.
Nutrients. 2017 Oct 25;9(11):1166. doi: 10.3390/nu9111166.
Although the relation of the gut microbiota to a development of autoimmune and inflammatory diseases has been investigated in various animal models, there are limited studies that evaluate the effect of probiotics in the autoimmune eye disease. Therefore, we aimed to investigate the effect of IRT-5 probiotics consisting of , , , , and on the autoimmunity of uveitis and dry eye and alloimmunity of corneal transplantation.
Experimental autoimmune uveitis was induced by subcutaneous immunization with interphotoreceptor-binding protein and intraperitoneal injection of pertussis toxin in C57BL/6 (B6) mice. For an autoimmune dry eye model, 12-weeks-old NOD.B10. mice were used. Donor cornea of B6 mice was transplanted into BALB/C mice. IRT-5 probiotics or phosphate buffered saline (PBS) were administered for three weeks immediately after induction of uveitis or transplantation. The inflammation score of the retinal tissues, dry eye manifestations (corneal staining and tear secretion), and graft survival were measured in each model. The changes of T cells were evaluated in drainage lymph nodes using fluorescence-activated cell sorting.
Retinal histology score in IRT-5 group of uveitis was lower than that in PBS group ( = 0.045). Ocular staining score was lower ( < 0.0001) and tear secretion was higher ( < 0.0001) in the IRT-5 group of NOD.B10. mice than that in the PBS group. However, the graft survival in the IRT-5 group was not different from those of PBS group. The percentage of regulatory T cells was increased in the IRT-5-treated dry eye models ( = 0.032). The percentage of CD8⁺IL-17 ( = 0.027) and CD8⁺ interferon gamma (IFNγ) cells ( = 0.022) were significantly decreased in the IRT-5-treated uveitis models and the percentage of CD8⁺IFNγ cells was markedly reduced ( = 0.036) in IRT-5-treated dry eye model.
Our results suggest that administration of IRT-5 probiotics may modulate clinical manifestations of autoimmunity in the eye, but not on alloimmunity of corneal transplantation.
虽然肠道微生物群与自身免疫和炎症性疾病的发展关系已在各种动物模型中进行了研究，但评估益生菌对自身免疫性眼病影响的研究有限。因此，我们旨在研究由 、 、 、 和 组成的 IRT-5 益生菌对葡萄膜炎和干眼症的自身免疫以及角膜移植的同种异体免疫的影响。
通过在 C57BL/6（B6）小鼠中皮下免疫感光细胞间结合蛋白和腹腔内注射百日咳毒素来诱导实验性自身免疫性葡萄膜炎。对于自身免疫性干眼症模型，使用 12 周龄的 NOD.B10. 小鼠。B6 小鼠的供体角膜被移植到 BALB/C 小鼠中。在葡萄膜炎或移植后立即立即用 IRT-5 益生菌或磷酸盐缓冲盐水（PBS）治疗 3 周。在每种模型中测量视网膜组织的炎症评分、干眼症表现（角膜染色和泪液分泌）和移植物存活率。使用荧光激活细胞分选术评估引流淋巴结中的 T 细胞变化。
葡萄膜炎 IRT-5 组的视网膜组织学评分低于 PBS 组（=0.045）。NOD.B10. 小鼠 IRT-5 组的眼部染色评分较低（<0.0001），泪液分泌较高（<0.0001），而 PBS 组则无差异。然而，IRT-5 组的移植物存活率与 PBS 组无差异。在 IRT-5 治疗的干眼症模型中，调节性 T 细胞的百分比增加（=0.032）。在 IRT-5 治疗的葡萄膜炎模型中，CD8⁺IL-17（=0.027）和 CD8⁺干扰素γ（IFNγ）细胞的百分比显著降低（=0.022），并且在 IRT-5 治疗的干眼症模型中 CD8⁺IFNγ细胞的百分比明显降低（=0.036）。
我们的结果表明，给予 IRT-5 益生菌可能调节眼部自身免疫的临床表现，但不能调节角膜移植的同种异体免疫。
