Interleukin-31 at the neuroimmune interface of pruritus and dermatitis
白介素 31 在瘙痒和皮炎神经免疫界面的作用
基本信息
- 批准号:10470809
- 负责人:
- 金额:$ 17.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-25 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAddressAdultAdvisory CommitteesAffectAfferent NeuronsAfferent PathwaysAllelesAllergensAlopeciaAnimalsAtopic DermatitisAwardBehaviorBiologicalBiological ProductsBiologyCD4 Positive T LymphocytesCaliforniaCellsChildChloroquineClinicalClinical TrialsCommunicationCouplesCutaneousDataDermatitisDermatologistDevelopmentDevelopment PlansDoctor of PhilosophyElementsEngineeringEnvironmentExanthemaExcoriationFoundationsFunctional disorderFutureGeneticGenetic EpistasisGoalsHTR2A geneHematopoieticHistamineImmuneImmune responseImmune systemInflammationInflammation MediatorsInflammatoryInterleukin-13Interleukin-4InterleukinsKnock-inLinkMapsMediatingMediator of activation proteinMentorshipMissionModelingMolecularMouse StrainsMusNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNerveNervous system structureNeurogenic InflammationNeuroimmuneNeuronsNeurosciencesPAR-2 ReceptorPainPathway interactionsPatient CarePatientsPatternPeptide HydrolasesPeripheralPhysiciansPopulationPostdoctoral FellowProductionPruritusRecombinant InterleukinsReporterResearchResourcesSan FranciscoScientistSensorySignal TransductionSkinSourceT-LymphocyteTRPV1 geneTestingTherapeuticTherapeutic antibodiesTissuesTrainingTransgenic AnimalsTransgenic OrganismsUniversitiesafferent nerveatopybehavior influencebehavioral responsecareer developmentcell typechronic inflammatory skinchronic itchcytokineeffective therapyeffector T celleosinophilexperimental studyimprovedin vivomast cellmouse geneticsmouse modelmultidisciplinaryneurotoxicnoveloverexpressionpsychosocialreceptorresponseskin disordertool
项目摘要
PROJECT SUMMARY/ABSTRACT
Despite the clinical and psychosocial burden of itch in atopic dermatitis (AD), effective treatment options
are limited. Interleukin-31 (IL-31), an inflammatory factor produced by skin T cells, has emerged as a powerful
mediator of both itch and rash. When administered to skin, IL-31 can trigger dermatitis and activate cutaneous
afferent sensory nerves to drive scratching behavior. Therapeutic antibodies directed against IL-31 and its
receptor, IL31RA, have shown promise in clinical trials for AD and chronic pruritus. Yet fundamental questions
about IL-31 biology remain. Which cells make IL-31? What pathways does IL-31 actuate in sensory afferent
neurons? How do IL-31 signals integrate with other pruritogenic pathways in the context of inflammation?
Improved definitions of the sources, pathways, and effector functions of IL-31 will substantially advance
mechanistic understanding of the links between inflammation and itch.
Dr. Fassett’s long-term research goal is to elucidate cellular and molecular mechanisms responsible for
atopy-associated pruritus. The objective of this proposal is to use genetic mouse models to address the in vivo
biology of IL-31 by examining the effects of endogenous IL-31 on cutaneous inflammation and pruritus sensory
pathways. Dr. Fassett’s central hypothesis is that IL-31 couples itch and rash via its combined effects on
pruritoceptive afferent pathways and cutaneous Th2 cytokine-mediated inflammation. Dr. Fassett will test this
hypothesis using three specific aims. In Aim 1, Dr. Fassett will use novel IL31-deficient animals and IL31-
tdTomato reporter animals to determine how multiple IL-31 source cell types functionally impact cutaneous Th2
inflammation in vivo. In Aim 2, she will elucidate the contribution of IL-31:IL31RA to atopy-associated
pruritoceptive pathways including itch sensation and neurogenic inflammation. In Aim 3, she will determine how
IL-31 alters afferent responses to other pruritogens, including Th2 cytokines. This project is relevant to the
mission of NIAMS because it explores the mechanism of action of IL-31, a biologic target of potentially great
therapeutic value for atopic dermatitis and for pruritus associated with other inflammatory skin diseases.
Dr. Fassett is an MD PhD-trained Dermatologist working as a post-doctoral research fellow at the University
of California, San Francisco. She is applying for a K08 Award to support her goal of becoming an independent
physician scientist. UCSF’s exceptional training environment will support her efforts. Critical elements of her
career development plan include mentorship by Dr. Mark Ansel, expert in cytokine biology and Th2 inflammation;;
co-mentorship by Dr. Allan Basbaum, expert in pain and itch;; guidance by a multidisciplinary advisory committee
including senior physician-scientists;; coursework in advanced experimental neuroscience;; and professional
development activities. Taken together, this career development plan will provide Dr. Fassett with a strong
foundation on which to build her growing expertise in the neuroimmune pathways that couple itch and rash.
项目总结/摘要
尽管特应性皮炎(AD)瘙痒的临床和心理负担,
白细胞介素-β 31(IL-β 31)是一种由皮肤T细胞产生的炎症因子,
当给予皮肤时,IL-131可引发皮炎并激活皮肤炎症。
针对IL-10 β 31及其受体的治疗性抗体
IL 31 RA在AD和慢性瘙痒症的临床试验中显示出了希望。
关于IL-131的生物学知识仍然存在。哪些细胞产生IL-131? IL-131在感觉传入中通过什么途径激活
神经元? 在炎症背景下,IL-131信号如何与其他促炎途径整合?
IL-131的来源、途径和效应器功能的改进定义将大大推进
对炎症和瘙痒之间联系的机械理解。
Fassett博士的长期研究目标是阐明细胞和分子机制,
该建议的目的是使用遗传小鼠模型来解决体内遗传性瘙痒症。
通过检测内源性IL-10 β 31对皮肤炎症和感觉瘙痒的作用,
Fassett博士的中心假设是,IL-131通过其对皮肤的联合作用,
免疫感受性传入通路和皮肤Th 2细胞因子介导的炎症。
在目标1中,Fassett博士将使用新的IL 31-β缺陷动物和IL 31-β缺陷动物。
tdTomato报告动物,以确定多种IL-131源细胞类型如何在功能上影响皮肤Th 2
在目的2中,她将阐明IL-131:IL-31 RA对特应性鼻炎相关的炎症的作用。
在目标3中,她将确定如何通过刺激性神经传导通路,包括瘙痒感觉和神经源性炎症。
IL-131改变了对其他促炎原的传入反应,包括Th 2细胞因子。
NIAMS的使命,因为它探索了IL-131的作用机制,IL-131是一种潜在的巨大的生物靶点。
对特应性皮炎和与其它炎性皮肤病相关的瘙痒症的治疗价值。
Fassett博士是一名医学博士,在大学担任博士后研究员,
来自加州,旧金山弗朗西斯科。她正在申请K 08奖,以支持她成为一个独立的目标
医生科学家。UCSF的特殊培训环境将支持她的努力。她的关键因素
职业发展计划包括由细胞因子生物学和Th 2炎症专家Mark Ansel博士指导;
由疼痛和瘙痒专家Allan Basbaum博士共同指导;由多学科咨询委员会指导
包括高级医师-神经科学家;高级实验神经科学的神经科学课程;神经科学和专业
发展活动。总的来说,这个职业发展计划将为Fassett博士提供一个强大的
在此基础上,她建立了越来越多的专业知识,在神经免疫途径耦合瘙痒和皮疹。
项目成果
期刊论文数量(0)
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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Marlys S Fassett其他文献
Marlys S Fassett的其他文献
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{{ truncateString('Marlys S Fassett', 18)}}的其他基金
Illuminating IL-31-producing cells in allergic skin disease
照亮过敏性皮肤病中产生 IL-31 的细胞
- 批准号:
10729476 - 财政年份:2023
- 资助金额:
$ 17.75万 - 项目类别:
Interleukin-31 at the neuroimmune interface of pruritus and dermatitis
白介素 31 在瘙痒和皮炎神经免疫界面的作用
- 批准号:
10240316 - 财政年份:2019
- 资助金额:
$ 17.75万 - 项目类别:
Interleukin-31 at the neuroimmune interface of pruritus and dermatitis
白介素 31 在瘙痒和皮炎神经免疫界面的作用
- 批准号:
10025166 - 财政年份:2019
- 资助金额:
$ 17.75万 - 项目类别:
Interleukin-31 at the neuroimmune interface of pruritus and dermatitis
白介素 31 在瘙痒和皮炎神经免疫界面的作用
- 批准号:
10684666 - 财政年份:2019
- 资助金额:
$ 17.75万 - 项目类别:
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