Elucidating the role of autocrine TNF signaling in maintaining human regulatory T cell identity

调节性T细胞是我们免疫系统中的一群细胞，负责控制所有其他免疫细胞，并抑制在对自身或无害因子做出反应时错误激活的免疫反应。尽管它们不到血液中所有细胞的1%，但没有它们我们就无法生存。因此，重要的是要了解控制其功能和维护的机制，以确保它们正常发挥功能，以避免自身免疫反应。我们已经确定了一种名为肿瘤坏死α（TNF α）的蛋白质是由调节性T细胞分泌的，这有点令人惊讶，因为这种蛋白质被认为主要导致炎症。如果我们从调节性T细胞中删除这种蛋白质，它们就无法增殖并保持其特性。我们假设调节性T细胞表达TNF α对于调节性T细胞的增殖和正常功能是重要的。我们将使用几种方法和与人类细胞和小鼠模型进行的实验的组合，以测试这一假设，回答两个问题：1）是什么机制，控制这种蛋白质的表达由调节性T细胞？2）调节性T细胞分泌的TNF α的功能是什么？该项目获得的结果将帮助我们了解调节性T细胞在健康个体和炎症性疾病中维持其功能和特性的机制。

Regulatory T cells are a population of cells from our immune system that are in charge of controlling all other immune cells and of inhibiting immune responses that are mistakenly activated in response to self or unharmful agents. Even though they are less than 1% of all the cells in the blood, we cannot survive without them. It is therefore important to understand the mechanisms that control their function and maintenance to ensure that they function properly to avoid autoimmune reactions. We have identified that a protein called Tumor Necrosis Alpha (TNFa) is secreted by regulatory T cells, which is somewhat surprising because this protein is thought to mainly contribute to inflammation. If we delete this protein from regulatory T cells, they are unable to proliferate and maintain their characteristics. We hypothesize that the expression of TNFa by regulatory T cells is important for the proliferation and proper function of regulatory T cells. We will use several approaches and a combination of experiments performed with human cells and mouse models to test this hypothesis by answering two questions: 1) what are the mechanisms that control the expression of this protein by regulatory T cells? And 2) What is the function of TNFa secreted by regulatory T cells? The results obtained in this project will help us understand the mechanisms that regulatory T cells utilize to maintain their function and characteristics in healthy individuals and in inflammatory diseases.