Role of DN T cells in colonic microbiota-immune system maturation

DN T 细胞在结肠微生物群免疫系统成熟中的作用

• 批准号: 9258021
• 负责人: LESLEY PASMAN
• 金额: $ 5.71万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9258021
• 关键词: Address; Agonist; Alpha Cell; Area; Autoimmune Process; Basic Science; Biochemical; Biological; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell physiology; Cells; Characteristics; Chemistry; Colon; Communicable Diseases; Complex; Data; Disease; Doctor of Philosophy; Environment; Flow Cytometry; Fractionation; Fusobacteria; Fusobacterium mortiferum; Future; Germ-Free; Gnotobiotic; Goals; Homeostasis; Human; Human Microbiome; Immune; Immune system; Immunity; Immunobiology; Immunology; Intestines; Knowledge; Leadership; Lymphoid Tissue; Microbiology; Modeling; Mus; Physiological; Population; Postdoctoral Fellow; Prevalence; Protein Analysis; Research; Role; Sensitivity Training Groups; Signal Transduction; Site; System; T-Lymphocyte; Techniques; Technology; Time; Tissues; Training; biomarker identification; commensal microbes; gastrointestinal epithelium; gut microbiota; improved; insight; knowledge base; member; microbial; microbial community; microbiome; microbiota; microorganism interaction; mouse model; new therapeutic target; peripheral blood; post-doctoral training; skills; tool; tool development; transcriptome sequencing

Project Summary `Double negative' (DN) T cells are an understudied group of T lymphocytes with unclear function. Preliminary data shows that these cells are specifically expanded in colonic lymphoid tissue when GF mice are monocolonized with specific members of the healthy human microbiota, especially Fusobacterium mortiferum. These cells are a physiologically large component of the intestinal T cell population, constituting ~30% of conventional colonic T cells, equal in proportion to CD4+ and CD8+ T cells. Despite this, they remain relatively poorly understood. The purpose of DN T cell expansion, as well as the general role of F. mortiferum in the healthy microbiota, is currently unknown. I propose that F. mortiferum educates the DN T cell population in the colonic lymphoid tissue towards a specific function that aids in maturation of the healthy microbiota-immune homeostasis. The goal of this proposal is to explore the function of these cells in the intestinal system of healthy wildtype host. Two approaches will be taken in this exploration: 1) characterization of DN T cells expanded in F. mortiferum monocolonization, and 2) biochemical fractionation of F. mortiferum to identify which specific microbial components are actively involved with DN T cell expansion. This will be tackled through my PhD expertise in immunobiology and infectious diseases, and expanded with my postdoctoral training in the microbiome with the Kasper lab's unique interface of microbiology, chemistry, and immunology. This study addresses two current unmet areas of basic research: the physiological purpose of DN T cells in the gut, and the role of Fusobacteria in the composition of healthy microbiota. Improvements in these two areas will help expand current understanding of the host immune-microbial interaction, and may also provide new targets for therapeutic manipulation of the intestinal immune composition.

项目总结