2005 Fiscal Year Final Research Report Summary
Mechanisms and treatments of autoimmune diseases by Th1/Th2 unbalance
| Project/Area Number |
15380210
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Applied veterinary science
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
HAYASHI Toshiharu Yamaguchi University, Faculty of Agriculture, Professor, 農学部, 教授 (90111484)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SATO Kouichi Yamaguchi University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (90205914)
KYUWA Shigeru The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (30177943)
YASUTOMI Yasuhiro Mie University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90281724)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Keywords | diabetes / lupus / tolerance / Th1 / Th2 / Gene therapy / autoimmune diseases / CD4^+CD25^+T cell |
|---|
| Research Abstract |
Summary consisted of 6 items listed bellow concerning mechanisms and treatments of autoimmune diseases by Th1/Th2 unbalance
[I].Lupus as Th1 disease : [1].in vivo CpG-ODN-treatment accelerated lupus nephritis during the preactive phase in lupus-prone female NZBxNZWF_1(model) mice, and IL-6 detection in the blood may be an indicator of the onset of the disease. Moreover, IFN-gamma may play a role in IL-6 production. [2].IL-1 and TNF-alfa, which are related to Th1 cytokines, may at least in part be responsible for the increased ICAM-1 expression on endothelium, in cutaneous microvessels, resulting in the vascular injury characterized by neutrophilic lekocytoclasis in B/WF1 mice. [3].CD4^+CD25^+ T cells may, at least in part, downregulate the development of glomerulonephritis during the preactive phase. [II].Type I diabete as Th1 disease. : [1] The systemic administration of IL-4 expressing plasmid DNA inhibited the development of insulitis with impaired glucose tolerance(IGT) in a dose dependent manner. [2]Adhesion molecules(ICAM-1/LFA-1) may be required for the differentiation of Th0 cells to Th1 cwlls, which mediate insulitis with IGT in Reo-2-infected suckling mice.[3].CD4^+CD25^+ T cells may, at least in part,maintain tolerance to Reo-2-triggered and CpG-ODN-induced prolonged mild Th1-depebdent auoimmune insulitis, leading to the overt diabetes.
Taken together, the studies suggest that Th2-cytokine expressing plasmid may applicable for a new therapy to lupus as Th1 disease. Moreover our system may give a novel model to elucidate the mechanisms of the development of overt diabetes from borderline diabetes in virus-triggered autoimmune type I diabetes in human.
|
