白细胞介素17介导致糖尿病性T细胞诱导的NOD小鼠糖尿病的发生

目的 研究白细胞介素17(IL-17)在致糖尿病性BDC2.5 T细胞转移性糖尿病发病中的作用.方法 通过注射转基因IL-17 BDC2.5 T细胞(IL-17组,n=6)、IL-17 siRNA BDC2.5 T细胞(silL-17组,n=5),观察高表达和低/无表达IL-17转基因BDC2.5 T细胞对NOD.scid小鼠转移性糖尿病的影响,进行小鼠胰岛组织学鉴定、脾脏和胰腺淋巴结染色和血浆细胞因子测定.非转基因BDC2.5 T细胞注射为对照组(n=8).结果 在观察期内,IL-17组小鼠全部发生糖尿病,而silL-17组和对照组则无一例发病.胰腺病理HE染色显示IL-17组小鼠出现严重的胰岛炎,胰岛受到破坏,结构模糊不清;而silL-17组小鼠胰腺仅表现为轻、中度胰岛炎,可见胰岛内散在的细胞浸润,胰岛组织结构基本完整,细胞形态正常.小鼠脾脏和淋巴结染色显示,IL-17组小鼠脾脏和胰腺淋巴结中CD11c+/CD11b+的树突细胞增殖显著高于silL-17组和对照组(均P＜0.01),且胰腺淋巴结中该细胞增殖显著高于脾脏.IL-17组小鼠血浆IL-17、肿瘤坏死因子α、γ-干扰素和白细胞介素6水平均显著高于siIL-17组和对照组(均P＜0.01),后两组间差异无统计学意义(P＞0.05).结论 BDC2.5 T细胞的IL-17高表达可显著加速NOD.scid小鼠发生转移性糖尿病,且与宿主树突细胞增殖和在胰腺淋巴结局部的聚集以及多种细胞因子作用有密切关系.

Interleukin-17 mediates the pathogenesis of diabetes induced by diabetogenic T lymphocytes in NOD mice

Objective To study the role of interleukin-17 (IL-17) expression in diabetogenic BDC2.5 T lymphocytes in transferring diabetes to NOD.scid mice.Methods With injection of IL-17and IL-17 siRNA transgenic BDC2.5 T lymphocytes to NOD.scid mice,the effects of the high-expressing or low/non-expressing IL-17 transgenic BDC2.5 T lymphocytes in transferring diabetes were observed.Islets histopathology,stain the spleens and pancreatic lymph node lymphocytes were compared,and plasma cytokines were determined.BDC2.5 T lymphocytes was injected in control group.Results By the end of the experiment,all of the NOD.scid mice injected IL-17 transfected BDC2.5 T lymphocytes grew diabetes,while the mice injected silL-17 transgenic BDC2.5 T lymphocytes and controls remained non-diabetic.Distinct severe insulitis and destruction of islets were found in NOD.scid mice injected IL-17 BDC2.5 T lymphocytes,but only mild or moderate insulitis in NOD.scid mice with injection of siIL-17 BDC2.5 T lymphocytes or BDC2.5 T lymphocytes.With stain of spleens lymphocytes and pancreatic lymph node lymphocytes,the proliferation of CD11c+/CD11b+ dendritric cells were increased in NOD.scid injected IL-17 BDC2.5 T lymphocytes than those injected IL-17 siRNA BDC2.5 T lymphocytes and control group (both P＜0.01).The plasma levels of IL-17,tumor necrosis factor-α,interferon-γ interleukin-6 were elevated in the mice injected IL-17 BDC2.5 T lymphocytes than the other two groups(P＜0.01),no difference existed between the latter two groups(P＞0.05).Conclusion Transferring BDC2.5 T lymphocytes with high IL-17 expression seems to speed up the development of diabetes in NOD.scid mice,which had a close relation to dentritic cells gathering in pancreatic lymph node and the mutual actions of multiple cytokines.