APCs and environmental cues for inflammation-linked Th17 immunity

APC 和炎症相关 Th17 免疫的环境线索

• 批准号: 9910614
• 负责人: Gianna Elena Hammer
• 金额: $ 48.73万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9910614
• 关键词: Antigen-Presenting Cells; Antigens; Autoimmune Process; Autoimmunity; Biochemistry; Biological Assay; CD4 Positive T Lymphocytes; Cell physiology; Cells; Consequentialism; Cues; Data; Disease; Engineering; Epithelial Cells; Gene Expression; Health; Homeostasis; Human; Immune Targeting; Immunity; In Situ; In Vitro; Inflammation; Inflammatory; Interleukin-17; Intestines; Knockout Mice; Link; Location; LoxP-flanked allele; Measures; Mediating; Microbe; Modeling; Molecular; Mouse Strains; Mus; NF-kappa B; Nature; Organ; Pathway interactions; Phenotype; Population; Regulation; Reporter; Role; Signal Transduction; Small Intestines; Specificity; T-Lymphocyte; T-cell receptor repertoire; Testing; Tissues; Vaccine Design; Work; base; conditional knockout; inflammatory disease of the intestine; innovation; insight; intestinal epithelium; langerin; macrophage; microorganism antigen; mouse model; new therapeutic target; novel; novel strategies; response; transcriptomics; translational impact

Summary of Work Understanding how antigen presenting cells (APCs) use environmental cues to influence T cell antigen specificity and function is a pressing issue since IL-17-producing CD4 T cells (Th17) can exist in two dichotomous states: 1) Th17 that exist in health and cause no inflammation (“Th17h”) and 2) Th17 that expand during autoimmune and inflammatory disease (“Th17i”). Because some tissues, like small intestine, naturally contain large numbers of Th17h cells, distinguishing Th17h and Th17i cells in these tissues has been a remarkable challenge. Consequentially, the origins, functions and even the existence of Th17i cells in these tissues have been highly debated. To begin to resolve this we took a focused look at Th17 cells in inflamed small intestine and identified populations of Th17i cells readily distinguishable from Th17h cells since these Th17i cells have distinct antigen specificity and localization than do Th17h cells. By all measures thus far these Th17i cells are exclusive to inflammation and do not appear to exist in conditions of health. With our new approach to distinguish Th17h and Th17i cells, the objective of this proposal is to understand the nature and origins of Th17i cells, and the environmental cues and APCs underpinning their expansion in inflammation.

工作总结 了解抗原提呈细胞(APC)如何利用环境线索影响T细胞抗原 特异性和功能是一个紧迫的问题，因为产生IL-17的CD4T细胞(Th17)可以存在于 二分状态：1)存在于健康中且不会引起炎症的Th17(“Th17h”)和2)膨胀的Th17 在自身免疫性和炎症性疾病期间(“Th17i”)。因为有些组织，比如小肠，自然地 含有大量的Th17h细胞，在这些组织中区分Th17h和Th17i细胞一直是一种 非同寻常的挑战。因此，Th17i细胞的起源、功能甚至存在于这些细胞中 纸巾一直备受争议。为了开始解决这个问题，我们重点观察了炎症中的Th17细胞 小肠和已鉴定的Th17i细胞群很容易与Th17h细胞区分开来，因为 与Th17h细胞相比，Th17i细胞具有明显的抗原特异性和定位。从目前为止的所有衡量标准来看，这些 Th17i细胞是炎症的专属细胞，在健康条件下似乎不存在。使用我们的新产品 区分Th17h和Th17i细胞的方法，这项建议的目的是了解 Th17i细胞的起源，以及支持它们在炎症中扩张的环境线索和APC。