髓系抑制性细胞和调节性T细胞在小鼠实验性结肠炎中的作用

Role of myeloid-derived suppressor cells and regulatory T cells in mouse models of ulcerative colitis

摘要:

目的探讨髓系抑制性细胞（MDSC）和调节性T 细胞（Treg 细胞）在小鼠溃疡性结肠炎发生、发展过程中的作用。方法使用5%右旋葡聚糖硫酸钠（DSS）溶液复制小鼠溃疡性结肠炎模型，每日观察小鼠体重和大便状况。DSS 处理3 和7 d 后处死小鼠，苏木精- 伊红染色法观察病理组织学变化，流式细胞仪检测脾脏和肠系膜淋巴结中MDSC 和Treg 细胞的表达。结果模型组小鼠于造模第4 天体重开始下降，有腹泻和血便，HE染色结果显示小鼠结肠出现黏膜损伤及炎症表现。与对照组和造模3 d组比较，造模7 d 组肠系膜淋巴结中Treg 细胞比例增加，而MDSC 比例降低；进一步观察MDSC 亚群变化发现，粒细胞型MDSC 在造模7 d组中比例下降，而单核细胞型MDSC则无改变。无论Treg细胞还是MDSC，脾脏中的水平3组比较差异无统计学意义。结论急性溃疡性结肠炎可导致MDSC降低和Treg细胞增高，可能与疾病的发生发展有关。

Abstract:

Objective To investigate the role of myeloid-derived suppressor cells (MDSC) and regulatory T(Treg) cells in development of ulcerative colitis. Methods Mouse models of ulcerative colitis were established with administration of 5%dextran sodium sulfate (DSS). Body weight and hematochezia were obtained daily.Mice were sacrificed 3 or 7 days post insult. Histological assessment of ulcerative colitis was graded with hematoxylin-eosin staining. The percentages of MDSC and Treg cells in the spleen and mesenteric lymph nodes were measured by flow cytometry. Results In animals treated with DSS, body weight loss, diarrhea and hematochezia were observed on the 4th day. Histological analysis revealed colonic mucosa damage and manifestation of inflammation. The amount of Treg cells was increased, whereas the amount of MDSC was decreased significantly in mesenteric lymph nodes in 7-day model group (P < 0.05). Further observation on the subsets of MDSC suggested that the percentage of granulocyte-like MDSC decreased in the 7-day model group ( P< 0.05) while no significant change of monocyte-like MDSC was observed among all the groups.There was no significant difference in the amount of Treg cells or MDSC in spleen among three groups.Conclusion Acute ulcerative colitis experiences decreased MDSC and increased Treg cells, which could contribute to the development of ulcerative colitis.