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在化学烧伤小鼠模型中,骨髓间充质干细胞影响分泌白细胞介素-17细胞的免疫谱。

Bone marrow-derived mesenchymal stem cells affect immunologic profiling of interleukin-17-secreting cells in a chemical burn mouse model.

作者信息

Lee Ja Young, Jeong Hyun Jeong, Kim Mee Kum, Wee Won Ryang

机构信息

Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea. ; Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea.

Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea.

出版信息

Korean J Ophthalmol. 2014 Jun;28(3):246-56. doi: 10.3341/kjo.2014.28.3.246. Epub 2014 May 19.

Abstract

PURPOSE

This study investigated interleukin (IL)-17-secreting cell involvement in sterile inflammation, and evaluated the effect of mesenchymal stem cells (MSCs) on IL-17-secreting cell immunologic profiling.

METHODS

Twenty mice were sacrificed at time points of 6 hours, 1 day, 1 week, and 3 weeks (each group, n = 5) after the cornea was chemically injured with 0.5N NaOH; IL-17 changes in the cornea were evaluated using enzyme-linked immunosorbent assay. Further, IL-17 secreting cells were assessed in the cervical lymph nodes by a flow cytometer. Rat MSCs were applied intraperitoneally in a burn model (n = 10), IL-17-secreting T helper 17 (Th17) cell and non-Th17 cell changes were checked using a flow cytometer in both cornea and cervical lymph nodes at 1 week, and compared with those in the positive control (n = 10).

RESULTS

IL-17 was highest in the cornea at 1 week, while, in the cervical lymph nodes, IL-17-secreting cells showed early increase at 6 hours, and maintained the increase through 1 day to 1 week, and levels returned to the basal level at 3 weeks. Specifically, the non-Th17 cells secreted IL-17 earlier than the Th17 cells. When the MSCs were applied, IL-17 secretion was reduced in CD3(+)CD4(-)CD8(-), CD3(+)CD4(+)CD8(-), and CD3(+) CD4(-)CD8(+) cells of the cervical lymph nodes by 53.7%, 43.8%, and 50.8%, respectively. However, in the cornea, IL-17 secretion of CD3(+)CD4(-)CD8(-) cells was completely blocked.

CONCLUSIONS

The results indicated that both IL-17-secreting non-Th17 and Th17 cells were involved in the chemical burn model, and MSCs appeared to mainly modulate non-Th17 cells and also partially suppress the Th17 cells.

摘要

目的

本研究调查了分泌白细胞介素(IL)-17的细胞在无菌性炎症中的作用,并评估了间充质干细胞(MSC)对分泌IL-17细胞免疫谱的影响。

方法

用0.5N氢氧化钠对角膜进行化学损伤后,在6小时、1天、1周和3周的时间点处死20只小鼠(每组,n = 5);采用酶联免疫吸附测定法评估角膜中IL-17的变化。此外,通过流式细胞仪评估颈淋巴结中分泌IL-17的细胞。在烧伤模型(n = 10)中腹腔注射大鼠MSC,在1周时使用流式细胞仪检测角膜和颈淋巴结中分泌IL-17的辅助性T细胞17(Th17)细胞和非Th17细胞的变化,并与阳性对照组(n = 10)进行比较。

结果

角膜中IL-17在1周时最高,而在颈淋巴结中,分泌IL-17的细胞在6小时时早期增加,并在1天至1周内持续增加,3周时水平恢复到基础水平。具体而言,非Th17细胞比Th17细胞更早分泌IL-17。应用MSC后,颈淋巴结中CD3(+)CD4(-)CD8(-)、CD3(+)CD4(+)CD8(-)和CD3(+)CD4(-)CD8(+)细胞中的IL-17分泌分别减少了53.7%、43.8%和50.8%。然而,在角膜中,CD3(+)CD4(-)CD8(-)细胞的IL-17分泌被完全阻断。

结论

结果表明,分泌IL-17的非Th17细胞和Th17细胞均参与了化学烧伤模型,MSC似乎主要调节非Th17细胞,也部分抑制Th17细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/4038731/b9e4f3bd9d32/kjo-28-246-g001.jpg

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