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The analysis of new mouse model for glomerulonephritis and an approach for Th1/Th2 cell regulation by transcription factors

新型肾小球肾炎小鼠模型分析及转录因子调控Th1/Th2细胞的方法

基本信息

批准号：
17590819
负责人：
YOH Keigyou
金额：
$ 1.73万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590819/
关键词：
T cell glomerulonephritis Th1 Th2

项目摘要

Flsky skin (fsn) mice develop glomerulonephritis, psoriasis, a high level of serum IgE, and severe anemia. Psoriasis is known to Th1 phenotype and a high level of IgE is Th2 phenotype. The transcription factors T-bet and GATA-3 are thought to be key regulators of Th1/Th2 differentiation. In this study, T-bet overexpressed fsn mice (T-bet fsn mice) and GATA-3 overexpressed fsn mice (GATA-3 fsn mice) were generated and analyzed with fsn mice about glomerulonephritis and Th1/Th2 subset. The results showing as following : 1. fsn mice showed CD4/CD8 imbalance. Thymus CD4+CD8+ T cells population in fsn mice was decreased than that of wild mice. 2. The proteinuria of T-bet fsn mice decreased than that of fsn mice. The results suggested that transcriptional regulation might effect the development of glomerulonephritis in fsn mice. 3. fsn mice showed Th2 dominant background in immunoglobulin subset analysis. 4. T-bet fsn mice showed Th1 dominant background in immunoglobulin subset analysis. The serum IgG1 level and IgG2a/IgG1 ratio of T-bet fsn mice was lower than those of fsn mice. 5. T-bet fsn mice did not prolong the survival rate than that of fsn mice. T-bet fsn mice, GATA-3 fsn mice, and fsn mice all died within 25 week-old. The results showed that T-bet overexpressed in fsn mice might improve glomerulonephritis, but not survival rate. The data suggested that Th1/Th2 background might not contribute the cause of death in fsn mice. The cause of death in fsn mice might be due to other reasons, such as severe anemia.

Flsky skin（fsn）小鼠发生肾小球肾炎、银屑病、高水平血清IgE和严重贫血。已知银屑病为Th 1表型，高水平的IgE为Th 2表型。转录因子T-bet和加塔-3被认为是Th 1/Th 2分化的关键调节因子。本研究建立了T-bet过表达的fsn小鼠（T-bet fsn小鼠）和加塔-3过表达的fsn小鼠（加塔-3 fsn小鼠），并与fsn小鼠进行了肾小球肾炎和Th 1/Th 2亚群的分析。结果表明：1. fsn小鼠表现为CD 4/CD 8失衡。fsn小鼠外周血CD 4 + CD 8 + T细胞数量较野生型小鼠减少。2. T-bet fsn小鼠尿蛋白较fsn小鼠减少。结果提示转录调控可能影响fsn小鼠肾小球肾炎的发生发展。3. fsn小鼠在免疫球蛋白亚群分析中显示Th 2优势背景。4. T-bet fsn小鼠在免疫球蛋白亚群分析中表现出Th 1优势背景。T-bet fsn小鼠血清IgG 1水平和IgG 2a/IgG 1比值低于fsn小鼠。5. T-bet fsn小鼠的存活率并没有比fsn小鼠延长。T-bet fsn小鼠、加塔-3 fsn小鼠和fsn小鼠均在25周龄内死亡。结果表明，在fsn小鼠中过表达T-bet可改善肾小球肾炎，但对存活率无明显影响。提示Th 1/Th 2本底可能不是fsn小鼠死亡的原因。fsn小鼠的死亡原因可能是其他原因，如严重贫血。