Clinical Effect of IRT-5 Probiotics on Immune Modulation of Autoimmunity or Alloimmunity in the Eye

Abstract

Background: 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 Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus reuteri, Bifidobacterium bifidum, and Streptococcus thermophilus on the autoimmunity of uveitis and dry eye and alloimmunity of corneal transplantation. Methods: 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.H2(b) 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. Results: Retinal histology score in IRT-5 group of uveitis was lower than that in PBS group (p = 0.045). Ocular staining score was lower (p < 0.0001) and tear secretion was higher (p < 0.0001) in the IRT-5 group of NOD.B10.H2(b) 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 (p = 0.032). The percentage of CD8(+)IL-17(hi) (p = 0.027) and CD8(+) interferon gamma (IFN gamma)(hi) cells (p = 0.022) were significantly decreased in the IRT-5-treated uveitis models and the percentage of CD8(+)IFN gamma(hi) cells was markedly reduced (p = 0.036) in IRT-5-treated dry eye model. Conclusion: 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.