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

Klrg1 调节性 T 细胞亚群在健康和疾病中的功能剖析

基本信息

批准号：
10287917
负责人：
Li-Fan Lu
金额：
$ 23.7万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10287917
关键词：
Ablation Affect Animal Model Antigens Autoimmune Autoimmune Diseases Autoimmunity Biological Cells Cellular biology Colitis Colon Data Development Differentiation Antigens Disease Dissection Employment Enterobacteria phage P1 Cre recombinase Exhibits Foundations Frequencies Future Gene Expression Profiling Genes Genetic Models Goals Health Heterogeneity Homeostasis Human Immune Immune System Diseases Immune Tolerance Immune response Immune system Immunologics Individual Inflammation Intestines Knowledge Lead Literature Mediating Methods Modeling Molecular Mus Natural Killer Cells Normal tissue morphology PTPRC gene Pathologic Peripheral Phenotype Physiological Population Prevalence Regulatory T-Lymphocyte Reporting Research Role Small Intestines Solid Spleen T-Cell Depletion T-Lymphocyte T-Lymphocyte Subsets Testing Tissues base differential expression effector T cell experience immune activation immunoregulation in vivo insight interest mouse model novel novel therapeutics pathogenic microbe peripheral tolerance single cell sequencing single-cell RNA sequencing transcriptomics

项目摘要

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.

在过去的二十年中，调节t（Treg）细胞已成为专门的免疫种群对免疫反应的负调节。但是，Treg的确切效应机制细胞介导的在特定免疫条件下特定组织微环境中的抑制仍然不完全理解。迄今为止，累积证据表明，类似于他们调节的常规t（TCONV）细胞，Treg细胞在表型和在功能上。除了控制不同类型的T细胞免疫的Treg细胞的异质性。反应，在许多非淋巴组织中存在明显的Treg细胞种群的存在也开始是感谢。在此提案中，尽管建立了一种新颖的鼠标模型，该模型可以使我们能够替换所需的Treg细胞子集以暂时控制的方式，我们将确定特定的细胞作用在两种生理学下维持周围组织稳态的表达Treg细胞种群表达KLRG1 和病理状况。此外，通过采用尖端的单细胞转录方法，我们将获得进一步的分子和细胞见解，以了解KLRG1+ Treg细胞耗竭对免疫的影响特定组织微环境中的系统以公正的方式。总的来说，我们拟议的研究将不仅提供了Treg细胞介导的免疫的KLRG1+ Treg细胞子集的全面评估调节，但也将促进对KLRG1+的潜在效应机制的更好理解 Treg细胞保持周围组织的稳态。完成本应用程序中提出的目标将毫无疑问，我们对免疫测量和对新理论的发展提供进一步的见解，是指靶向Treg细胞以治疗广泛的人类免疫疾病范围。