Characterization of innate and IgE-mediated mast cell functions in honeybee venom allergy using Collaborative Cross mice
使用 Collaborative Cross 小鼠表征蜜蜂毒液过敏中的先天和 IgE 介导的肥大细胞功能
基本信息
- 批准号:10681390
- 负责人:
- 金额:$ 52.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-22 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AccountingAffinityAllergensAllergicAllergic DiseaseAllergic ReactionAnaphylaxisAnimalsAntigensBacteriaBindingBiological ModelsCD4 Positive T LymphocytesCRISPR/Cas technologyCandidate Disease GeneCell DegranulationCell physiologyCell secretionCellsCessation of lifeClinicalCoupledCytoplasmic GranulesDevelopmentDiseaseDoseExposure toFoodGenesGeneticGenetic VariationGrowth FactorHost DefenseHumanHymenopteraHypersensitivityIgEIgE ReceptorsIgG1ImmuneImmune responseImmunityIn VitroIndividualInflammationInflammation MediatorsInsect StingInsectaLifeLipidsMapsMeasuresMediatingMediatorMedicineModelingModificationMusOutcomeParasitesPassive Cutaneous AnaphylaxisPathologyPeptide HydrolasesPersonsPharmaceutical PreparationsPharmacologic SubstancePhenotypePredispositionPrevention approachProbabilityProductionProliferatingQuantitative Trait LociReactionRegulatory PathwayResearchResistanceResolutionRoleSeveritiesShockSigns and SymptomsSnake VenomsStaphylococcus aureusSting InjuryStrongyloidesSystemTissuesToxic effectVariantVenomsWorkZebrafishcardiovascular collapsechemokineconfocal imagingcrosslinkcytokineexperienceexperimental studyfunctional genomicsgenetic analysisgenetic linkage analysisgenomic locusimprovedmast cellnovelpathogenic bacteriapreventresponsescreeningtechnology platformtrait
项目摘要
PROJECT SUMMARY/ABSTRACT
We will use Collaborative Cross (CC) mice to define how genetic traits influence innate and/or IgE-mediated
responses of mast cells (MCs) to honeybee venom. In IgE-dependent allergic reactions, crosslinking of MC
high affinity IgE receptors (i.e., FceRI) by the binding of bivalent or multivalent allergen to antigen-specific IgE
activates MCs to secrete three major classes of products: 1) preformed mediators stored in cytoplasmic
granules, 2) newly synthesized lipid-derived mediators, and 3) cytokines, chemokines and growth factors.
These MC products are responsible for many of the signs and symptoms of allergic diseases. MC activation,
with or without the involvement of IgE, is also thought to contribute to the inflammation, tissue damage, and
even fatal shock induced by envenomation. Components of hymenoptera venoms (e.g., honeybee venom),
pharmaceutical agents, and foods are the most common triggers for anaphylaxis in humans. Many people have
been sensitized to hymenoptera venoms and some unfortunate individuals react after exposure to such insect
stings with serious systemic reactions and even fatal anaphylaxis. However, recent experiments in mice and
zebra fish demonstrate that MC-derived proteases can degrade animal venoms and diminish their toxicity. Also,
IgE/FceRI-mediated MC activation can enhance the survival of mice challenged with honeybee venom or a
snake venom, or with S. aureus bacteria. Yet the benefits of “allergic immune responses”, mediated by IgE/MC-
dependent mechanisms, have not been widely recognized. While the exact mechanisms determining whether
the outcomes of hymenoptera envenomation are detrimental or favorable have been elusive, we know that
genetic factors can significantly influence the development, progression, and severity of allergy and
anaphylaxis. We hypothesize that genetic traits, by modulating the strength and/or composition of MC
responses to honeybee venom and/or the Th2-IgE-MC immune axis, can influence the outcomes of
honeybee stings. In this project, we propose to use genetically diverse CC mice to identify genetic modifiers
regulating MC functions in insect venom allergy. In Aim 1, we will screen a panel of CC mice for their
susceptibility to the toxicity of honeybee venom, development and features of venom-specific type 2 immunity,
and induction of MC activation with or without crosslinking of venom-specific IgE/FceRI. We will also perform
quantitative trait locus (QTL) mapping of the venom-induced phenotypes in CC mice to identify distinct genetic
loci and novel regulators associated with MC-dependent susceptibility vs. resistance to honeybee venom. In
Aim 2, we will confirm, in mouse MCs, important regulators of MC functions that are identified by screening CC
mice using QTL analysis to assess the involvement of these regulators in innate and/or IgE-mediated MC
functions. We think that the identification of genetic modifiers that distinguish beneficial vs. harmful effects of
innate and/or allergic immune responses to honeybee venom will improve the treatment of severe reactions to
insect venom and probably other disorders in which IgE and MCs have a critical role.
1
项目总结/文摘
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)
Conditional neutrophil depletion challenges their contribution to mouse models of anaphylaxis.
条件性中性粒细胞耗竭挑战了它们对小鼠过敏反应模型的贡献。
- DOI:10.1111/all.15738
- 发表时间:2023
- 期刊:
- 影响因子:12.4
- 作者:Stackowicz,Julien;Gillis,CaitlinM;Godon,Ophélie;Iannascoli,Bruno;Conde,Eva;Leveque,Edouard;Worrall,WilliamPM;Galli,StephenJ;Bruhns,Pierre;Reber,LaurentL;Jönsson,Friederike
- 通讯作者:Jönsson,Friederike
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Stephen Joseph Galli其他文献
Stephen Joseph Galli的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Stephen Joseph Galli', 18)}}的其他基金
Characterization of degranulation regulators in human mast cells
人类肥大细胞脱颗粒调节剂的表征
- 批准号:
10284390 - 财政年份:2021
- 资助金额:
$ 52.46万 - 项目类别:
Characterization of innate and IgE-mediated mast cell functions in honeybee venom allergy using Collaborative Cross mice
使用 Collaborative Cross 小鼠表征蜜蜂毒液过敏中的先天和 IgE 介导的肥大细胞功能
- 批准号:
10331200 - 财政年份:2021
- 资助金额:
$ 52.46万 - 项目类别:
Characterization of degranulation regulators in human mast cells
人类肥大细胞脱颗粒调节剂的表征
- 批准号:
10415223 - 财政年份:2021
- 资助金额:
$ 52.46万 - 项目类别:
Role of nociceptive sensory neuron/mast cell interactions in cutaneous allergic inflammation
伤害性感觉神经元/肥大细胞相互作用在皮肤过敏性炎症中的作用
- 批准号:
9363714 - 财政年份:2017
- 资助金额:
$ 52.46万 - 项目类别:
Role of nociceptive sensory neuron/mast cell interactions in cutaneous allergic inflammation
伤害性感觉神经元/肥大细胞相互作用在皮肤过敏性炎症中的作用
- 批准号:
9922209 - 财政年份:2017
- 资助金额:
$ 52.46万 - 项目类别:
RabGEF1 in MyD88 signaling, skin immunity, and atopic dermatitis
RabGEF1 在 MyD88 信号传导、皮肤免疫和特应性皮炎中的作用
- 批准号:
9293893 - 财政年份:2015
- 资助金额:
$ 52.46万 - 项目类别:
RabGEF1 in MyD88 signaling, skin immunity, and atopic dermatitis
RabGEF1 在 MyD88 信号传导、皮肤免疫和特应性皮炎中的作用
- 批准号:
9068815 - 财政年份:2015
- 资助金额:
$ 52.46万 - 项目类别:
RabGEF1 in MyD88 signaling, skin immunity, and atopic dermatitis
RabGEF1 在 MyD88 信号传导、皮肤免疫和特应性皮炎中的作用
- 批准号:
8960798 - 财政年份:2015
- 资助金额:
$ 52.46万 - 项目类别:
Integrated Genomic and Functional Studies of Tolerance Therapy for Peanut Allerg
花生过敏耐受疗法的综合基因组和功能研究
- 批准号:
8699865 - 财政年份:2013
- 资助金额:
$ 52.46万 - 项目类别:
Integrated Genomic and Functional Studies of Tolerance Therapy for Peanut Allerg
花生过敏耐受疗法的综合基因组和功能研究
- 批准号:
8462368 - 财政年份:2013
- 资助金额:
$ 52.46万 - 项目类别:
相似海外基金
Construction of affinity sensors using high-speed oscillation of nanomaterials
利用纳米材料高速振荡构建亲和传感器
- 批准号:
23H01982 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Affinity evaluation for development of polymer nanocomposites with high thermal conductivity and interfacial molecular design
高导热率聚合物纳米复合材料开发和界面分子设计的亲和力评估
- 批准号:
23KJ0116 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Platform for the High Throughput Generation and Validation of Affinity Reagents
用于高通量生成和亲和试剂验证的平台
- 批准号:
10598276 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
Development of High-Affinity and Selective Ligands as a Pharmacological Tool for the Dopamine D4 Receptor (D4R) Subtype Variants
开发高亲和力和选择性配体作为多巴胺 D4 受体 (D4R) 亚型变体的药理学工具
- 批准号:
10682794 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233343 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
Standard Grant
Collaborative Research: DESIGN: Co-creation of affinity groups to facilitate diverse & inclusive ornithological societies
合作研究:设计:共同创建亲和团体以促进多元化
- 批准号:
2233342 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
Standard Grant
Molecular mechanisms underlying high-affinity and isotype switched antibody responses
高亲和力和同种型转换抗体反应的分子机制
- 批准号:
479363 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
Operating Grants
Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime
解构 T 细胞抗原识别:亲和力与键寿命的分离
- 批准号:
10681989 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
CAREER: Engineered Affinity-Based Biomaterials for Harnessing the Stem Cell Secretome
职业:基于亲和力的工程生物材料用于利用干细胞分泌组
- 批准号:
2237240 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
Continuing Grant
ADVANCE Partnership: Leveraging Intersectionality and Engineering Affinity groups in Industrial Engineering and Operations Research (LINEAGE)
ADVANCE 合作伙伴关系:利用工业工程和运筹学 (LINEAGE) 领域的交叉性和工程亲和力团体
- 批准号:
2305592 - 财政年份:2023
- 资助金额:
$ 52.46万 - 项目类别:
Continuing Grant














{{item.name}}会员




