Engineering the Skin Microenvironment to Promote Allergen Tolerance
改造皮肤微环境以促进过敏原耐受性
基本信息
- 批准号:10613869
- 负责人:
- 金额:$ 60.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdoptedAdrenal Cortex HormonesAllergensAllergic Contact DermatitisAnti-Inflammatory AgentsAntigen PresentationAntigensAutoantigensAutomobile DrivingBiocompatible MaterialsBiomedical EngineeringCD14 geneCholecalciferolChronicClinical TrialsContact DermatitisCutaneousDataDendritic CellsDermalDermatologicDermatologyDinitrochlorobenzeneDoseDrug Delivery SystemsEgg ProteinsEngineered skinEngineeringEvaluationExposure toFOXP3 geneGoalsHaptensHealthHumanHypersensitivityImmune System DiseasesImmune systemImmunologyInflammationInflammatoryInflammatory ResponseInterleukin-2Lymphoid TissueMapsMediatingModelingMusNeedlesNickelPhenotypePolymersPopulationProcessProteinsRegulatory T-LymphocyteReporterRhus radicansSirolimusSkinSkin TissueSpecificitySystemT cell differentiationT-Cell ActivationT-LymphocyteTechnologyTherapeuticTimeTissuesTranslationsUltraviolet Raysanalogchemical allergenclinical candidateclinical translationcontrolled releasecostdesigndihydroxy-vitamin D3draining lymph nodeeffector T cellefficacy evaluationexperienceexperimental studyfabricationin vivolymph node microenvironmentmigrationmouse modelmultidisciplinarynovelparticlepreventprophylacticresearch clinical testingresponseskin disordertranslational approachtranslational studyurushiol
项目摘要
ABSTRACT
Allergic contact dermatitis (ACD) is a destructive T-cell-mediated inflammation of the skin,
resulting from repeated contact with allergens (e.g. nickel or poison ivy). ACD is one of the most
common skin diseases, afflicting roughly 15-20 percent of the population, with annual costs in
excess of $2 billion in the U.S. alone. Aside from avoiding known allergens when possible, current
treatments involve non-specific anti-inflammatories that transiently suppress cutaneous
inflammation, but fail to address the underlying immune dysfunction. In contrast, our bodies
ordinarily employ highly specific mechanisms to suppress excessive inflammation, many of which
are mediated by regulatory T cells (Tregs). Studies have shown that enhancing allergen or
autoantigen-specific populations of Tregs can promote tolerance, or hyporesponsiveness, and
ameliorate tissue-destructive inflammation. Information present in the local microenvironments
where dendritic cells encounter or present allergen dictates whether T cells will become
inflammatory effector T cells (Teff) or protective Tregs.
The goal of the studies we propose is to develop an antigen specific strategy to prevent
and treat contact dermatitis. We recently demonstrated that sustained local delivery of TReg-
Inducing (“TRI”) factors and allergens with degradable, polymeric microparticles (MPs) or
microneedle arrays (MNAs) expands allergen-specific Tregs and inhibits Teff differentiation
during cutaneous allergen exposure, thereby promoting allergen-specific tolerance. In this
proposal, we will induce tolerance by engineering local skin or lymph node microenvironments to
promote Treg differentiation. To that end, we will leverage our multidisciplinary team’s combined
experience and capabilities to specifically deliver Treg-inducing factors to defined
microenvironments of the skin or skin draining lymph nodes using microneedle arrays and micro-
sized controlled release systems. Importantly, our experiments include translational studies
focusing on human skin that are designed to enable rapid translation of this strategy to clinical
trials.
摘要
过敏性接触性皮炎(ACD)是一种破坏性的T细胞介导的皮肤炎症,
由于反复接触过敏原(如镍或毒葛)。ACD是世界上
常见的皮肤病,约占人口的15- 20%,每年的费用为
仅在美国就超过20亿美元除了尽可能避免已知的过敏原外,目前
治疗涉及非特异性抗炎药,其暂时抑制皮肤炎症,
炎症,但未能解决潜在的免疫功能障碍。相反,我们的身体
通常采用高度特异性的机制来抑制过度炎症,其中许多
是由调节性T细胞(T细胞)介导的。研究表明,增强过敏原或
自身抗原特异性的Tcl 4群体可促进耐受性或低反应性,
改善组织破坏性炎症。局部微环境中存在的信息
树突状细胞遇到或呈递过敏原的位置决定了T细胞是否会成为
炎性效应T细胞(Teff)或保护性Teff。
我们提出的研究目标是开发一种抗原特异性策略,
治疗接触性皮炎我们最近证明了TReg的持续本地交付-
诱导(“TRI”)因子和过敏原与可降解的聚合物微粒(MP)或
微针阵列(MNAs)扩增变应原特异性Teff并抑制Teff分化
在皮肤过敏原暴露期间,从而促进过敏原特异性耐受。在这
我们将通过设计局部皮肤或淋巴结微环境来诱导耐受性,
促进Treg分化。为此,我们将利用我们的多学科团队的联合力量
有经验和能力专门提供Treg诱导因子,
皮肤或皮肤引流淋巴结的微环境,
大小控制释放系统。重要的是,我们的实验包括翻译研究
专注于人类皮肤,旨在将该策略快速转化为临床应用
审判
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Louis D Falo其他文献
Louis D Falo的其他文献
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{{ truncateString('Louis D Falo', 18)}}的其他基金
Multiscale, Multimodal Analysis of Skin and Spatial Cell Organization
皮肤和空间细胞组织的多尺度、多模式分析
- 批准号:
10708913 - 财政年份:2022
- 资助金额:
$ 60.81万 - 项目类别:
Multiscale, Multimodal Analysis of Skin and Spatial Cell Organization
皮肤和空间细胞组织的多尺度、多模式分析
- 批准号:
10530827 - 财政年份:2022
- 资助金额:
$ 60.81万 - 项目类别:
Engineering the Skin Immune System to Induce Systemic Immune Responses
改造皮肤免疫系统以诱导全身免疫反应
- 批准号:
10363729 - 财政年份:2021
- 资助金额:
$ 60.81万 - 项目类别:
Project 3: Localized microneedle-directed combination immunotherapy for cSCC
项目3:局部微针定向联合免疫治疗cSCC
- 批准号:
10469637 - 财政年份:2021
- 资助金额:
$ 60.81万 - 项目类别:
Project 3: Localized microneedle-directed combination immunotherapy for cSCC
项目3:局部微针定向联合免疫治疗cSCC
- 批准号:
10683759 - 财政年份:2021
- 资助金额:
$ 60.81万 - 项目类别:
Engineering the Skin Immune System to Induce Systemic Immune Responses
改造皮肤免疫系统以诱导全身免疫反应
- 批准号:
10561663 - 财政年份:2021
- 资助金额:
$ 60.81万 - 项目类别:
Project 3: Localized microneedle-directed combination immunotherapy for cSCC
项目3:局部微针定向联合免疫治疗cSCC
- 批准号:
10270233 - 财政年份:2021
- 资助金额:
$ 60.81万 - 项目类别:
Engineering the Skin Microenvironment to Promote Allergen Tolerance
改造皮肤微环境以促进过敏原耐受性
- 批准号:
9753923 - 财政年份:2018
- 资助金额:
$ 60.81万 - 项目类别:
MNA Delivery of Neurokinin 1 Receptor Antagonists to Treat Atopic Dermatitis
MNA 递送神经激肽 1 受体拮抗剂治疗特应性皮炎
- 批准号:
10171787 - 财政年份:2017
- 资助金额:
$ 60.81万 - 项目类别:
Manipulating Cutaneous Neuroimmunity to Treat Contact Dermatitis
操纵皮肤神经免疫治疗接触性皮炎
- 批准号:
9302683 - 财政年份:2015
- 资助金额:
$ 60.81万 - 项目类别:
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