Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells
Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells
批准号:
9384627
负责人:
Daniel J Campbell
金额:
$50.32万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-06-20 至 2022-05-31
关键词:
AddressAnimal ModelBehaviorBloodCCR8 geneCD4 Positive T LymphocytesCD69 antigenCD8B1 geneCell Differentiation processCellsCommunitiesCutaneousDevelopmentEngineeringFOXP3 geneFibroblastsGPR2 geneGranulocyte-Macrophage Colony-Stimulating FactorHome environmentHomeostasisHomingHumanImmunityIn VitroIndividualInfectionInfection preventionInflammationInflammatoryInflammatory ResponseIntegrinsInterleukin-13IrritantsLymphocyte antigenMediatingMemoryMolecularMolecular TargetMusNormal tissue morphologyOrganismPhenotypePopulationProductionRegulationRegulatory T-LymphocyteRoleSkinSkin TissueSterilitySymbiosisT memory cellT-LymphocyteTestingTherapeuticTissue EngineeringTissue GraftsTissuesToxic Environmental SubstancesViralWorkWound Healingantimicrobialantimicrobial peptidebasecellular targetingchemokine receptorcombatcytokinehumanized mouseinnovationinsightinterleukin-22keratinocytemacrophagemicroorganismmigrationmonocytemouse modelnovelpathogenperipheral bloodpreventresponseskin disordertissue repairtrafficking
中文摘要
项目摘要
与其保持屏障完整性和预防感染的功能一致,皮肤是
专门的T细胞群的数量,不仅可以对抗感染,还可以协同工作,帮助
维持正常组织动态平衡,促进伤口修复。然而,尽管在以下方面取得了重大进展
了解皮肤免疫,不同群体皮肤T细胞的特定功能,他们
在维持正常皮肤动态平衡方面的作用,以及对皮肤炎症性疾病的贡献
人们对此知之甚少。在这方面,依赖动物模型可能是有问题的,因为
人类和小鼠皮肤的结构差异,以及皮肤之间缺乏直接的对应关系
这些物种中的T细胞群。此外,尽管嗜皮性T细胞可以很容易地在
外周血基于皮肤淋巴细胞抗原(CLA)的表达,发育和
血液中这些细胞与皮肤中不同数量的T细胞的功能关系仍然很差
明白了。
我们已经在健康受试者的外周血中发现了一种新的CLA CD4T细胞群
表达CD103整合素并产生IL-22、GM-CSF和IL-13的新细胞因子组合
激活(CD103 CLAHI细胞)。有趣的是,这种细胞因子组合也是由表型
类似于表皮CD103、CLA、CD69、TRM在皮肤本身。基于IL-22促进的能力
嗨
角质形成细胞的增殖、迁移和抗菌肽的产生以及GM-CSF和IL-13的作用
成纤维细胞,并介导单核细胞和巨噬细胞向“交替激活”细胞的分化
促进组织修复,我们假设血液中的CD103CLAHI T细胞代表着循环
CD103 CLAHI TRM的一部分,这些细胞有助于协调宿主保护和创伤
皮肤组织损伤后的愈合反应。因此,这些细胞有可能成为
以治疗的方式促进无菌伤口的愈合并优化其发展和功能
工程组织移植物。在这个提案中,我们将使用体外分析和创新的人源化小鼠
验证这些假说的模型,评估CD103CLAHI的发育起源和运输行为
并确定它们在皮肤组织修复反应中的功能。
英文摘要
Project Summary
Consistent with its functions in maintaining barrier integrity and preventing infection, the skin is home to a
number of specialized T cell populations that not only combat infection but also work in concert to help
maintain normal tissue homeostasis and promote wound repair. However, despite significant advances in
understanding cutaneous immunity, the specific functions of different populations of cutaneous T cells, their
roles in maintaining normal skin homeostasis, and contributions to inflammatory diseases of the skin remain
poorly understood. In this respect, reliance on animal models can be problematic due to fundamental
structural differences in the skin in humans vs. mice, and a lack of direct correspondence between cutaneous
T cell populations in these species. Additionally, although skin-tropic T cells can be readily identified in
peripheral blood based on their expression of the cutaneous lymphocyte antigen (CLA), the developmental and
functional relationship of these cells in the blood with the different populations of T cells in the skin is still poorly
understood.
We have identified a novel population of CLA+CD4+ T cells in the peripheral blood of healthy subjects that
expresses the CD103 integrin and produces the novel cytokine combination of IL-22, GM-CSF and IL-13 upon
activation (CD103+CLAhi cells). Interestingly, this cytokine combination is also produced by phenotypically
similar epidermal CD103 CLA CD69 TRM in the skin itself. Based on the ability of IL-22 to promote
+ hi +
keratinocyte proliferation, migration and production of antimicrobial peptides, and GM-CSF and IL-13 to act on
fibroblasts, and to mediate the differentiation of monocytes and macrophages into `alternatively activated' cells
that promote tissue repair, we hypothesize CD103+CLAhi T cells in the blood represent a recirculating
fraction of CD103+CLAhi TRM, and that these cells help coordinate the host-protective and wound
healing responses following tissue damage in the skin. As such, these cells have the potential to be
manipulated therapeutically to promote sterile wound healing and to optimize the development and function of
engineered tissue grafts. In this proposal, we will use in vitro analyses and innovative humanized mouse
models to test these hypotheses, assessing the developmental origins and trafficking behavior of CD103+CLAhi
cells and determining their function during cutaneous tissue-repair responses.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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Targeting the IL-2/regulatory T cell axis for autoimmune disease prevention in realistic animal models
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依托单位:
Functional specialization of Foxp3+ regulatory T cells
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依托单位:
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批准号:7655225
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资助金额:$41.18万
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财政年份:2009
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Homing and Homeostasis of Regulatory T cells
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依托单位:
海外基金