Functional dissection of the Klrg1+ regulatory T cell subset in health and diseases

在过去的二十年中，调节性T（Treg）细胞已经成为一种专用的免疫群体，对免疫系统的免疫调节至关重要。 免疫反应的负调节。尽管如此，Treg的精确效应机制 在特定免疫条件下，在特定组织微环境中的细胞介导的抑制 仍然不完全理解。迄今为止，越来越多的证据表明，类似于 它们调节的传统T（Tconv）细胞，Treg细胞在表型和 功能上。除了控制不同类型T细胞免疫的Treg细胞的异质性外， 在免疫应答中，许多非淋巴组织中不同Treg细胞群的存在也开始受到影响。 赞赏.在这项提议中，虽然建立了一种新的小鼠模型，可以让我们消耗一种 我们将以时间控制的方式确定所需Treg细胞亚群的细胞作用， Klrg1表达Treg细胞群在维持外周组织稳态中的作用 和病理条件。此外，通过采用尖端的单细胞转录组学方法，我们 将获得进一步的分子和细胞见解Klrg1+ Treg细胞耗竭对免疫系统的影响， 系统在特定组织微环境中以无偏的方式。总的来说，我们提出的研究将 不仅提供了Treg细胞介导的免疫反应中Klrg1+ Treg细胞亚群的全面评估， 调节，但也将有助于更好地了解潜在的效应机制，Klrg1+ Treg细胞维持外周组织稳态。实现本申请中提出的目的将 毫无疑问地扩展了我们对免疫调节中不同Treg细胞亚群的基本知识， 为靶向Treg细胞的新治疗手段的发展提供了进一步的见解，以治疗广泛的 一系列人类免疫系统疾病

In the past two decades, regulatory T (Treg) cells have emerged as a dedicated immune population crucial for the negative regulation of immune responses. Nonetheless, the precise effector mechanisms underlying Treg cell-mediated suppression in a specific tissue microenvironment under a particular immunological condition remains incompletely understood. To date, accumulating evidence has suggested that similar to the conventional T (Tconv) cells they regulate, Treg cells come in “different flavors” both phenotypically and functionally. In addition to the heterogeneity of the Treg cells that control different types of T cell immune responses, the presence of distinct Treg cell populations in many nonlymphoid tissues have also started to be appreciated. In this proposal, though establishing a novel mouse model that could allow us to deplete a desired Treg cell subset in a temporally controlled manner, we will determine the cellular role of a specific Klrg1-expressing Treg cell population in maintaining peripheral tissue homeostasis under both physiologic and pathologic conditions. Moreover, by employing a cutting-edge single-cell transcriptomic approach, we will gain further molecular and cellular insights into the impact of Klrg1+ Treg cell depletion on the immune system in a particular tissue microenvironment in an unbiased manner. Collectively, our proposed studies will not only provide a comprehensive assessment of the Klrg1+ Treg cell subset in Treg cell-mediated immune regulation but will also facilitate a better understanding of the potential effector mechanisms by which Klrg1+ Treg cells maintain peripheral tissue homeostasis. Accomplishing the aims proposed in this application will undoubtedly extend our fundamental knowledge of a distinct Treg cell subset in immune regulation and provide further insights into the development of new therapeutic means targeting Treg cells to treat a wide range of human immune disorders.