O. Gal-9 regulated cytokine expression in BD mice
Ⅴ. CONCLUSION
In conclusion, the frequencies of Tim-1(+) cells in BD mice were down-regulated compared to BDN mice. Tim-1 vector administration to BD mice improved the BD-like symptoms and decreased the severity score through up-regulation of Treg cells and down-regulation of pro-inflammatory cytokines. In addition, treatment with siTim-4 up-regulated Treg cells, and improved the BD-like symptoms, which were related to the expression of Tim-1 and Tim-4 with Tim-1-Tim-4 interaction. Furthermore, Tim-4 siRNA down-regulated the level of IL-17, might be involved to the improvement of BD-like symptoms.
Consequently, regulation of Tim-1 and Tim-4 was effective to improve the BD-like symptoms in mice.
The frequencies of Tim-3 in BD mice were significantly higher than normal and BDN mice. On the other hand, the frequencies of Gal-9 in BD mice were lower than in normal and BDN mice. After treatment with Gal-9, BD-like symptoms were improved, and the disease severity score was decreased. Gal-9 induced expression of cell death-related molecules, such as Annexin V(+)PI(-) apoptotic marker, granzyme B, and CD107a were increased in BD mice. In addition, Gal-9 increased Treg cells, and CD11c(+) DCs, but decreased cell-cell adhesion factor CD34(+) cells. Additionally, Gal-9 also decreased pro-inflammatory cytokines such as TNF-α, IL-6, and IL-17 in BD mice. Taken together, these findings indicate that Gal-9 could be a potential therapeutic agent for chronic inflammatory diseases, including BD.
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- 70 - - 국문요약 –
단순포진 바이러스로 유도한 베체트병 마우스 모델에서 T cell immunoglobulin mucin domain (Tim) 의 역할
아주대학교 대학원 의생명과학과 심 주 아
(지도교수 : 손성향)
T cell immunoglobulin mucin domain (TIM) 단백질은 T 세포의 활성과 tolerance를 조절한다. TIM family는 천식, 알레르기, 자가면역질환에 대한 감수성이 높은 표식자로 알려져 있다. TIM-1은 면역반응 조절과 자가면역질환을 일으키는데 중요한 역할을 하며, TIM-4는 TIM-1의 ligand로 알려져 있다. Tim-1과 Tim-4의 상호작용은 Th 세포 반응의 조절과 Th1/Th2 사이토카인의 균형을 조절한다고 보고되었다. TIM-3와 TIM-3 ligand 인 galectin-9 (Gal-9) 의 상호작용은 Th1 면역반응을 특이적으로 저해한다고 알려져 있다.
베체트병은 만성 염증질환으로 재발성 구강궤양, 외음부궤양, 피부 및 안증상 등이 특징인 질병이다. 베체트병은 여러증상들이 동시에 발병하거나 초기 피부 점막 증상이 호전과 악화를 거듭하다 관절 증상, 안 증상, 신경계 증상까지 발전할 수 있다. 특히 안 증상은 대표적인 베체트병 주 증상으로 실명이라는 심각한 후유증을 초래할 수 있다. 이러한 증상을 조절할 수 있는 방법으로, 본
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연구에서는 단순포진 바이러스로 유도한 베체트병 마우스 모델을 이용하여 Tim과의 연관성을 알아보고자 하였다. 우선 Tim-3 ligand인 Gal-9은 베체트병 마우스모델의 증상 군이 무증상 군 (바이러스 접종 후 증상이 나타나지 않은 군) 에 비하여 낮게 발현되었고, 반대로 Tim-3와 Tim-4는 높게 발현되었다. 그 발현의 차이가 증상 변화에 연관이 있는지 알아보기 위해 베체트병 마우스 모델에 Tim-1 vector를 투여한 결과 대조군과 비교하여 증상이 호전되었고 severity score는 감소하였다. Tim-4 siRNA를 투여한 후 증상이 완화되는 것을 관찰하였고
연구에서는 단순포진 바이러스로 유도한 베체트병 마우스 모델을 이용하여 Tim과의 연관성을 알아보고자 하였다. 우선 Tim-3 ligand인 Gal-9은 베체트병 마우스모델의 증상 군이 무증상 군 (바이러스 접종 후 증상이 나타나지 않은 군) 에 비하여 낮게 발현되었고, 반대로 Tim-3와 Tim-4는 높게 발현되었다. 그 발현의 차이가 증상 변화에 연관이 있는지 알아보기 위해 베체트병 마우스 모델에 Tim-1 vector를 투여한 결과 대조군과 비교하여 증상이 호전되었고 severity score는 감소하였다. Tim-4 siRNA를 투여한 후 증상이 완화되는 것을 관찰하였고