权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Microbial regulation of the keratinocyte AHR

角质形成细胞 AHR 的微生物调节

基本信息

批准号：
10599330
负责人：
Elizabeth Anne Grice
金额：
$ 55.72万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10599330
关键词：
Adhesions Agonist Antibiotics Aryl Hydrocarbon Receptor Atopic Dermatitis Bacterial Infections Biochemical Biology Calcipotriene Cells Chronic Collaborations Cutaneous Data Defect Disease Ensure Epithelium Flowers Functional disorder Genetic Transcription Germ-Free Goals Homeostasis Human In Vitro Infection Infection prevention Infectious Skin Diseases Inflammation Inflammatory Injury Innate Immune Response Ligands Mediating Mediator Microbe Modeling Molecular Mus Names Ovalbumin Pathology Pathway interactions Pattern recognition receptor Permeability Pharmacodynamics Poison Predisposition Prevention Receptor Activation Receptor Signaling Regulation Relapse Research Role Skin Staphylococcus aureus Staphylococcus aureus infection Symbiosis Testing Therapeutic Tight Junctions Tissues Tryptophan Xenobiotics antimicrobial antimicrobial peptide aryl hydrocarbon receptor ligand commensal bacteria dysbiosis efficacy evaluation host microbiota improved in vivo injury recovery insight keratinocyte microbial microbial colonization microbial community microbiota mouse model multiple omics novel pathogen prevent receptor repaired safety assessment skin barrier skin disorder skin lesion

项目摘要

PROJECT SUMMARY The complexity of microbial communities inhabiting the healthy human skin have been illuminated in recent years, as well as signatures associated with inflammatory skin diseases such as atopic dermatitis. However, the molecular and biochemical mechanisms that mediate microbial symbiosis with the skin are not well understood. We recently found that homeostatic skin barrier function, epidermal differentiation, and recovery from injury are dependent on the microbiota in mice. These effects were mediated by the keratinocyte aryl hydrocarbon receptor (AHR). The AHR is a ligand-dependent xenobiotic receptor of foreign/toxic substances that is also known to regulate epidermal differentiation, tight junction/adhesion, and antimicrobial innate immune responses. The objective of this project is to identify and characterize microbial ligands of the AHR, and to test their utility in treating skin barrier dysfunction and infection. Epidermal barrier dysfunction is a key feature of atopic dermatitis, a common skin disorder characterized by chronic and relapsing, itchy, inflamed, skin lesions and dysbiotic microbiota. To test the hypothesis that commensal bacteria mediate AHR signaling to promote skin barrier integrity and defense, we propose three aims. 1) Define microbial mechanisms of keratinocyte AHR regulation that promote barrier repair; 2) Establish pharmacodynamic actions of microbial AHR ligands to promote skin barrier function and antimicrobial defense; and 3) Evaluate microbial AHR ligands in treatment of epidermal barrier dysfunction and S. aureus infection in murine models. Findings from these studies will provide novel, accessible targets to promote skin barrier function and repair, while advancing fundamental understanding of cutaneous host-microbiota interactions.

项目总结近年来，人类健康皮肤中微生物群落的复杂性已被阐明。几年来，以及与特应性皮炎等炎症性皮肤病有关的特征。然而，介导微生物与皮肤共生的分子和生化机制还不是很好。明白了。我们最近发现，动态平衡的皮肤屏障功能，与表皮分化、修复是否受到伤害取决于小鼠体内的微生物区系。这些效应是由角质形成细胞芳基介导的。烃受体(AHR)。AHR是一种外源/有毒物质的配体依赖性异生受体这也是已知的调节表皮分化、紧密连接/粘连和先天抗菌药物。免疫反应。本项目的目标是鉴定和鉴定AHR的微生物配体，并测试它们在治疗皮肤屏障功能障碍和感染方面的有效性。表皮屏障功能障碍是一个关键特应性皮炎的特征，是一种常见的皮肤病，其特征是慢性且复发，发痒，发炎，皮肤损伤和微生物区系失调。为了验证共生细菌介导AHR信号的假设为了促进皮肤屏障的完整性和防御，我们提出了三个目标。1)定义微生物机制促进屏障修复的角质形成细胞AHR调节；2)建立微生物的药效学作用促进皮肤屏障功能和抗菌防御的AHR配体；以及3)评估微生物AHR配体用于治疗小鼠表皮屏障功能障碍和金黄色葡萄球菌感染。来自这些的发现研究将提供新的、可接近的靶点，以促进皮肤屏障的功能和修复，同时对皮肤宿主-微生物区系相互作用的基本了解。