Functional Dissection of Regulatory Myeloid Cells in Microbe-Immune Crosstalk in Skin
皮肤微生物免疫串扰中调节性骨髓细胞的功能剖析
基本信息
- 批准号:10830131
- 负责人:
- 金额:$ 6.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-01 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:AntigensBacteriaBehaviorCD4 Positive T LymphocytesCell physiologyCutaneousDataDendritic CellsDiseaseDissectionEngineered skinFutureGnotobioticHidradenitis SuppurativaHomeostasisHumanImmuneImmune ToleranceLigandsMaintenanceMeasuresMediatingMicrobeMyeloid CellsPathway interactionsPhenotypePopulationProcessRegulatory T-LymphocyteRoleSignal TransductionSiteSkinSymbiosisSystemTherapeuticTissuesTransgenic MiceWorkcell typechronic inflammatory skincommensal bacteriacommensal microbeshigh dimensionalityimmunoregulationinnovationmouse modelmutantnovelreceptorresponsesingle cell analysisskin disordertool
项目摘要
PROJECT SUMMARY
Establishment and maintenance of local immune homeostasis is essential for the integrity and function of body
barrier tissues. This process involves partnership between the tissue and the commensal microbes inhabiting
these sites. We have demonstrated that regulatory T cells (Tregs) are key to establishing immune tolerance to
skin commensal bacteria, and that type 2 conventional dendritic cells (cDC2s) are a critical, understudied
population that mediate the regulatory response to skin commensals. Specifically, our data suggest that cDC2s
capture commensal antigens more readily and prime commensal-specific CD4+ T cells more efficiently than
other DC subsets. After phagocytosing commensal bacteria, cDC2s display a mature-regulatory (mreg)
phenotype and preferentially support commensal-specific Tregs via a mechanism that may involve Myd88
signaling in DCs. The work proposed here will build on our preliminary observations to investigate how
commensal bacteria support the mreg phenotype of cDC2s and their ability to promote skin homeostasis
through commensal-specific immune tolerance. We will use engineered skin commensal bacteria mutants,
gnotobiotic and transgenic mouse models, high dimensional single cell analyses, novel tools to measure cDC2
priming of bacteria-specific CD4+ T cells and unique ex vivo systems to study human skin immune cell
function. Combining these will allow us to elucidate how host receptor pathways respond co-operatively to
bacterial ligands to promote immune homeostasis and in what manner these responses differ in skin disease,
specifically hidradenitis suppurativa. The proposed studies will use innovative approaches to define the role of
cDC2s in cutaneous immune regulation and identify the bacterial molecules and host pathways that regulate
these processes. The results will enhance our understanding of how bacteria partner to support skin
homeostasis, determine how this is altered in disease states, and inform future therapeutic strategies targeting
host-commensal interactions.
项目摘要
局部免疫稳态的建立和维持对机体的完整性和功能至关重要
屏障组织这一过程涉及组织和栖息在组织中的微生物之间的伙伴关系。
这些网站。我们已经证明,调节性T细胞(T细胞)是建立免疫耐受的关键,
皮肤细菌和2型常规树突状细胞(cDC 2)是一种关键的、研究不足的细胞,
介导对皮肤细胞的调节反应的群体。具体来说,我们的数据表明,cDC 2
更容易地捕获肿瘤抗原,更有效地引发肿瘤特异性CD 4 + T细胞,
其他DC子集。在吞噬肠道细菌后,cDC 2显示出成熟调节(mreg)
表型,并通过可能涉及Myd 88的机制优先支持膀胱特异性TcB
DC中的信号。这里提出的工作将建立在我们的初步观察,以调查如何
皮肤细菌支持cDC 2的mreg表型及其促进皮肤稳态的能力
通过直肠特异性免疫耐受。我们将使用工程皮肤细菌突变体,
gnotobiotic和转基因小鼠模型,高维单细胞分析,测量cDC 2的新工具
细菌特异性CD 4 + T细胞的引发和独特的离体系统以研究人皮肤免疫细胞
功能结合这些将使我们能够阐明宿主受体途径如何协同响应
细菌配体促进免疫稳态以及这些反应在皮肤病中的不同方式,
特别是化脓性汗腺炎。拟议的研究将采用创新的方法来确定
cDC 2在皮肤免疫调节中的作用,并鉴定调节皮肤免疫的细菌分子和宿主途径。
这些过程。研究结果将增强我们对细菌如何支持皮肤的理解
稳态,确定这是如何改变疾病状态,并告知未来的治疗策略,
宿主-宿主相互作用
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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Tiffany Crawford Scharschmidt其他文献
Tiffany Crawford Scharschmidt的其他文献
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{{ truncateString('Tiffany Crawford Scharschmidt', 18)}}的其他基金
Functional Dissection of Regulatory Myeloid Cells in Microbe-Immune Crosstalk in Skin
皮肤微生物免疫串扰中调节性骨髓细胞的功能剖析
- 批准号:
10605160 - 财政年份:2022
- 资助金额:
$ 6.4万 - 项目类别:
Functional Dissection of Regulatory Myeloid Cells in Microbe-Immune Crosstalk in Skin
皮肤微生物免疫串扰中调节性骨髓细胞的功能剖析
- 批准号:
10337996 - 财政年份:2022
- 资助金额:
$ 6.4万 - 项目类别:
Elucidating mechanisms of tolerance to commensal skin bacteria
阐明对共生皮肤细菌的耐受机制
- 批准号:
9753932 - 财政年份:2015
- 资助金额:
$ 6.4万 - 项目类别:
Elucidating mechanisms of tolerance to commensal skin bacteria
阐明对共生皮肤细菌的耐受机制
- 批准号:
8947751 - 财政年份:2015
- 资助金额:
$ 6.4万 - 项目类别:
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