Studies on autommune diseases in OSM deficient mice

OSM缺陷小鼠自身免疫性疾病的研究

基本信息

批准号：
18390119
负责人：
MIYAJIMA Atsushi
金额：
$ 10.39万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390119/
关键词：
knockout mouse autoimmune disease cytokine dendritic cells macrophage

项目摘要

Systemic lupus erythematosus (SLE) is a typical systemic autoimmune disease caused by immunological disorders and exhibits various clinical phenotypes. However, the mechanism of SLE development still remains unclear. We found that mice deficient for Oncostatin M (OSM), a member of IL-6 family, exhibit increased serum autoantibody levels and glomerulonephritis, we characterized OSM deficient mice to understand a cause of SLE. Histological analysis revealed that inflammation was observed in the lung and spleen and activated T cells infiltrated into the lung. Furthermore, arthritis of hind paw was observed in OSM-deficient male mice. These results indicated that OSM-deficient mice spontaneously develop SLE with inflammation in multiple organs. To address the relationship between OSM and autoimmunity, we examined the thymus of OSM-deficient mice and found thymic hypoplasia and altered thymic architecture. While T cells developed normally, numerous apoptotic thymocytes were detected in OSM-deficient thymus. Development of unique thymic macrophages with strong phagocytic activity was impaired in OSM-deficient mice, suggesting that autoantigens derived from thymus may be a cause of autoantibody production. Th1 response in peripheral immune response against LPS was augmented in OSM-deficient mice due to dysregulation of dendritic cells (DCs), indicating correlation of Th1 polarization and development of glomerulonephritis. To further analyze the abnormality of DC activation, we tried to identify factors involved in DC regulation by microarray analysis using OSM-deficient DCs. Currently, we are investigating functions of some candidate genes.

全身性红斑狼疮（SLE）是由免疫疾病引起的典型全身性自身免疫性疾病，表现出各种临床表型。但是，SLE发育的机制仍然不清楚。我们发现缺乏IL-6家族成员Oncostatin M（OSM）的小鼠表现出增加的血清自身抗体水平和肾小球肾炎，我们表征了OSM缺乏小鼠以了解SLE的原因。组织学分析表明，在肺和脾脏中观察到炎症，并激活的T细胞浸润到肺中。此外，在OSM缺陷型雄性小鼠中观察到后爪的关节炎。这些结果表明，OSM缺陷型小鼠在多个器官中会自发发育炎症。为了解决OSM与自身免疫性之间的关系，我们检查了OSM缺陷小鼠的胸腺，发现胸腺低质和改变胸腺造成体系结构。虽然T细胞正常发展，但在OSM缺陷胸腺中检测到许多凋亡的胸腺细胞。在OSM缺陷型小鼠中会损害具有强吞噬活性的独特胸腺巨噬细胞的发展，这表明源自胸腺的自身抗原可能是自身抗体产生的原因。由于树突状细胞的失调（DC），在OSM缺陷型小鼠中对LPS的外周免疫反应中的Th1反应增加了，这表明TH1 TH1极化和肾小球肾炎的发展相关。为了进一步分析DC激活的异常，我们试图通过使用OSM缺陷DC进行微阵列分析来识别DC调节涉及的因素。目前，我们正在研究某些候选基因的功能。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Isolation and characterization of p75^<NTR> positive cells from mouse fetal liver.

来自小鼠胎儿肝脏的p75^<NTR>阳性细胞的分离和表征。

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Suzuki K.;Tanaka M.;Watanabe N.;Miyajima A.
通讯作者：
Miyajima A.

Oncostatin M Receptor-b Signaling Limits Monocytic Cell Recruitment in Acute Inflammation

制瘤素 M 受体 -b 信号传导限制急性炎症中单核细胞的募集

DOI：
发表时间：
2008
期刊：
J. Immunol 181(3)
影响因子：
0
作者：
Hams E;Colmont C. S.;Dioszeghy V.;Hammond V. J.;Fielding C. A.;Williams A. S.;Tanaka M.;Miyajima A.;Taylor P. R.;Topley N.;Jones S. A.
通讯作者：
Jones S. A.

IL-18 produced by thymic epithelial cells induces the development of dendritic cells with CDllb in the fetal thymus.

胸腺上皮细胞产生的IL-18诱导胎儿胸腺中具有CDllb的树突状细胞的发育。