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: 10544146
• 负责人: Gianna Elena Hammer
• 金额: $ 42.33万
• 依托单位: UNIVERSITY OF UTAH
• 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 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10544146
• 关键词: Antigen-Presenting Cells; Antigens; Autoimmune Diseases; Autoimmunity; Biochemistry; Biological Assay; CD4 Positive T Lymphocytes; Cell physiology; Cells; Cues; Data; Disease; Engineering; Epithelial Cells; Gene Expression; Health; Homeostasis; Human; IL17 gene; Immune Targeting; Immunity; In Situ; In Vitro; Inflammation; Inflammatory; Intestines; Knockout Mice; Link; Location; LoxP-flanked allele; Macrophage; Measures; Mediating; Microbe; Modeling; Molecular; Mouse Strains; Mus; NF-kappa B; Nature; Organ; Pathway interactions; Phenotype; Population; Reaction; Regulation; Reporter; Role; Signal Transduction; Small Intestines; Sorting; Specificity; T cell receptor repertoire sequencing; T-Lymphocyte; T-cell receptor repertoire; Testing; Tissues; Vaccine Design; Work; conditional knockout; empowerment; gut inflammation; innovation; insight; intestinal epithelium; langerin; 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.

工作概要 了解抗原呈递细胞（APC）如何使用环境线索影响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CD 4 T细胞（Th 17）可以存在于两个细胞中， 二分状态：1）Th 17，其存在于健康中并且不引起炎症（“Th 17 h”），和2）Th 17，其扩增 在自身免疫性和炎性疾病（“Th 17 i”）期间。因为有些组织，比如小肠， 含有大量的Th 17 h细胞，区分这些组织中的Th 17 h和Th 17 i细胞一直是一个很好的方法。 了不起的挑战因此，Th 17 i细胞的起源、功能甚至存在于这些细胞中， 组织一直备受争议。为了开始解决这个问题，我们重点观察了炎症患者中的Th 17细胞。 小肠和鉴定的Th 17 i细胞群容易与Th 17 h细胞区分，因为这些 Th 17 i细胞比Th 17 h细胞具有不同的抗原特异性和定位。到目前为止，所有这些措施 Th 17 i细胞是炎症的专属细胞，在健康状况下似乎不存在。选用我们的 Th 17 h和Th 17 i细胞的区分方法，本提案的目的是了解Th 17 h和Th 17 i细胞的性质， Th 17 i细胞的起源，以及支持其在炎症中扩张的环境线索和APC。

项目成果

Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.

• DOI: 10.3389/fimmu.2021.661290
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Huang HI;Jewell ML;Youssef N;Huang MN;Hauser ER;Fee BE;Rudemiller NP;Privratsky JR;Zhang JJ;Reyes EY;Wang D;Taylor GA;Gunn MD;Ko DC;Cook DN;Chandramohan V;Crowley SD;Hammer GE
• 通讯作者: Hammer GE

A binary module for microbiota-mediated regulation of γδ17 cells, hallmarked by microbiota-driven expression of programmed cell death protein 1.

• DOI: 10.1016/j.celrep.2023.112951
• 发表时间: 2023-08-29
• 期刊: Cell reports
• 影响因子: 8.8