Investigation of the generation and functional maturation of regulatory T cells in vivo

本项目旨在从基因水平揭示免疫耐受的基本分子机制。免疫耐受是适应性免疫系统的独特属性，可抑制过度或不必要的免疫反应，从而防止自身免疫性疾病和过敏的发生。它在癌症的发展中也很重要，因为免疫耐受的机制抑制抗肿瘤免疫，从而促进恶性肿瘤的发展。调节性T细胞（Treg）是免疫耐受的核心参与者。Treg抑制其他T细胞的活动，从而阻止和解决T细胞的反应。Treg在基础免疫学和临床免疫学中被广泛研究，它们在自身免疫性疾病、过敏、器官移植排斥反应中发挥抑制不良免疫反应的作用。另一方面，Treg的消耗可以增强抗肿瘤免疫。然而，Treg的抑制机制尚不完全清楚，这种认识的缺乏阻碍了Treg介导的免疫调节在临床实践中的有效应用。转录因子Foxp3是Treg的关键因子，它控制Treg的分化，是Treg抑制活性所必需的。因此，虽然Treg的抑制机制尚不完全清楚，但研究foxp3介导的T细胞调控的分子机制是一种很有前途的方法。在本项目中，我们将研究Foxp3在基因水平上调控Treg抑制功能的分子机制，以及T细胞对抗原的反应如何促进Treg的分化和成熟。该项目旨在将可转移的知识和技术应用于工业，包括制药业。在基因水平上了解免疫耐受的机制和Treg的抑制机制不仅对科学进步有重要意义，而且对开发新的免疫抑制药物和疫苗具有重要意义。我们的目标是利用该项目的研究结果来提高新药开发筛选过程的效率。这项研究的结果将有益于广泛的科学界，并有助于人类和动物的健康和福祉。此外，该研究将为系统生物学提供新的框架，可用于许多生物学领域。

This project aims to reveal the fundamental molecular mechanisms of immunological tolerance at the gene level. Immunological tolerance is a unique attribute of the adaptive immune system and suppresses excessive or unnecessary immune responses and thereby prevents the development of autoimmune disease and allergy. It is also important in the development of cancer, as the mechanisms of immunological tolerance suppress anti-tumour immunity, and thereby contribute to the development of malignancies. Regulatory T cells (Treg) are a central player of immunological tolerance. Treg suppress the activities of other T cells and thereby prevent and resolve the T cell response. Treg have been extensively studied in basic and clinical immunology, and they play roles in suppressing unwanted immune responses in autoimmune diseases, allergy, organ transplant rejection. On the other hand, the depletion of Treg can increase anti-tumour immunity. However, the suppressive mechanism of Treg is not fully known, and this lack of understanding prevents the effective application of Treg-mediated immune regulation to clinical practice.The transcription factor Foxp3 is the key factor of Treg: it controls Treg differentiation and is required for the suppressive activity of Treg. Thus, although the suppressive mechanism of Treg is not fully known, it is a promising approach to investigate the molecular mechanisms of Foxp3-mediated T cell regulation. In this project, we will investigate the molecular mechanisms of how Foxp3 controls the suppressive function of Treg at gene level, and how T cell response to antigens promote the differentiation and maturation of Treg.The project aims to obtain transferable knowledge and technology to industry, including the pharmaceutical industry.The understanding of the mechanism of immunological tolerance and the suppressive mechanisms of Treg at the gene level is important not only for scientific progress but also for patency and for the development of new immunosuppressive drugs and vaccines. We also aim to use the findings of the project to improve the efficiency of the screening processes in the development of new drugs. The findings of this study will benefit broad scientific communities and contribute to health and well-being of humans and animals. In addition, this study will provide novel frameworks for systems biology, which can be used in many biological areas.