调节性树突状细胞对白细胞介素-10缺陷小鼠结肠炎模型的治疗作用

Therapeutic Effect of Regulatory Dendritic Cells on Interleukin-10-deficient Mouse Colitis Model

背景:目前认为克罗恩病(CD)的主要病理机制是黏膜反应性T细胞过度增生和活化。调节性树突状细胞(DCreg)对CD4^+T细胞增殖具有强烈抑制作用。目的:探讨DCreg对病理改变与人类CD类似的白细胞介素(IL)-10缺陷小鼠结肠炎模型的治疗作用。方法:以小鼠内皮型脾脏基质细胞诱导CD117阳性骨髓来源造血前体细胞分化为DCreg.通过观察其对CD4^+T细胞增殖的抑制作用进行质控。予IL-10基因敲除小鼠腹腔注射DCreg 2×10~6/只,每周采集血清测定IL-6和肿瘤坏死因子(TNF)-α水平,第8周取肠组织行组织病理学检查和IL-6、TNF-α水平测定。结果:经DCreg治疗后,62.5%(5/8)的小鼠结肠黏膜腺体轻度增生,未见明显免疫细胞浸润.37.5%(3/8)肠道黏膜组织结构接近正常;对照组小鼠结肠黏膜腺体增生明显,伴免疫细胞浸润和成纤维细胞增生。治疗组小鼠血清和结肠黏膜组织培养上清IL-6和TNF-α水平较对照组显著降低。结论:DCreg过继回输对缓解IL-10缺陷小鼠结肠炎具有明显疗效。

Background： Crohn＇s disease （CD） is a chronic inflammatory bowel disease caused by excessive proliferation and activation of mucosal reactive T cells. It has been reported recently that regulatory dendritic cells （DCreg） have an intensive inhibitory effect on the proliferation of CD4^＋ T cells. Aims： To investigate the therapeutic effect of DCreg on interleukin （IL）-10-deficient mouse model, of which the intestinal pathological changes are similar to those of human CD. Methods： DCreg was induced by mouse endothelial splenic stromal cells from CD117 positive marrow hematopoietic progenitors and its regulatory effect was tested by inhibiting CD4^＋ T cells proliferation. DCreg was transferred intraperitoneally into IL-10 gene knockout mice at a dosage of 2×10^6 cells per mouse. The serum levels of IL-6 and tumor necrosis factor （TNF）-α of the treated mice and the controls were tested every week. At the 8th week after treatment, the intestinal tissues were collected to evaluate the histopathological changes and the mucosal levels of IL-6 and TNF-α. Results： After treatment with DCreg, 5 （62.5%） mice had a slight glandular hyperplasia with few immunocytes infiltrating in the colonic mucosa, 3 （37.5%） had no colonic mucosal inflammation. However, all the control mice had severe glandular hyperplasia with obvious immunocytes infiltration and fibroblast proliferation. The levels of IL-6 and TNF-α in the serum and the cultured supernatant of colonic mucosal tissues decreased remarkably in the treated mice as compared with those in the controls. Conclusions： DCreg transfer is effective in relieving the IL-10-deficient mice colitis.