Themis in Type II Diabetes

描述（由申请人提供）：Themis（意为“参与选择的胸腺细胞表达分子”）是一种新发现的基因和蛋白，在未成熟的胸腺细胞中高表达，在成熟的T细胞中也有较低水平的表达。它是一个功能未知的小基因家族的成员。Themis缺乏小鼠会变得肥胖，并出现葡萄糖耐受不良和血清胰岛素升高，这表明Themis表达与预防脂肪组织炎症（导致代谢综合征和II型糖尿病（T2D））之间存在关系。最近发现T细胞在这一过程中起着重要作用。此外，通过基因组学鉴定，Themis与血清胰岛素水平存在因果关系，对T2D具有保护作用。本研究将探讨Themis在不同谱系的T细胞中的表达如何影响T细胞参与肥胖反应中的脂肪炎症，以及T2D之前的代谢综合征。它将测试代谢综合征和T2D的发展是如何因Themis的丧失而加剧的，以及其作用机制和所涉及的特异性T细胞亚群。

DESCRIPTION (provided by applicant): Themis (for "Thymocyte expressed molecule involved in selection") is a recently- discovered gene and protein that is highly expressed in immature thymocytes, and is also expressed at a lower level in mature T cells. It is a member of a small gene family of unknown function. Themis-deficient mice become obese and develop glucose intolerance and increased serum insulin, suggesting a relationship between Themis expression and prevention of the inflammation of adipose tissue that leads to metabolic syndrome and type II diabetes (T2D). T cells have recently been shown to be important in this process. Moreover, Themis was identified by genomics as showing a causal relationship to serum insulin level, with a protective effect against T2D. This proposal will investigate how expression of Themis in T cells of different lineages affects T cell involvement in adipose inflammation in response to obesity, and the metabolic syndrome that precedes T2D. It will test how the metabolic syndrome and development of T2D is exacerbated by loss of Themis, and the mechanism of action and specific T cell subsets involved. PUBLIC HEALTH RELEVANCE: The epidemic of obesity and Type II diabetes are becoming extremely important factors to the public health of the US and other developed nations. This project aims to understand the role of T cells in the initiation of the metabolic syndrome that leads to type II diabetes using a new mouse model.