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

Abstract

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. Key words: Interleukin 17; NOD mice; T lymphocytes; Diabetes mellitus