Endothelial regulation of IL17 producing T effector cell migration
内皮调节产生 IL17 的 T 效应细胞迁移
基本信息
- 批准号:8515502
- 负责人:
- 金额:$ 23.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-01 至 2015-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdhesionsAutoimmune DiseasesAwardBehaviorBiological AssayCCL20 geneCD4 Positive T LymphocytesCell Adhesion MoleculesCellsCytokine SignalingDataDiseaseE-SelectinEffector CellEndotheliumFundingGoalsHelper-Inducer T-LymphocyteHomingIL17 geneImmune System DiseasesIn VitroInfectionInflammationInflammatoryInstructionIntercellular adhesion molecule 1Interleukin-17KnowledgeLigandsMediatingMethodsModelingMusOrganP-SelectinPathologicPathologyPhasePhenotypePhysiologicalProcessRegulationResearch DesignResearch Project GrantsSiteSurfaceT-LymphocyteT-Lymphocyte SubsetsTNF geneTechniquesTh1 CellsTissuesVascular Endothelial CellWorkbasecell motilitycell typechemokinechemokine receptorin vivoin vivo Modelmicrobialmigrationmonolayerresponse
项目摘要
Different subsets of effector T ceils contribute in distinct ways to various pathologic conditions. Their
migration into tissues is a highly regulated process that involves interactions of the T cells with
vascular endothelial cells. IL-17 producing T helper cells (Th17), a newly defined T cell subset that
is pro-inflammatory, can contribute to the inflammatory pathology of organ specific autoimmune
diseases, as well as to protective responses against certain microbial infections. The overall aim of
this project is to study the regulation of migration of Th17 cells into inflammatory sites with the goal
of determining if their homing into tissues can be specifically targeted in therapeutically useful ways.
Based on data generated during the K99 funding period, my working hypothesis is that Th17 cells
have a different migratory phenotype than Th1 cells, a T cell type that also promotes inflammation. I
have established several new in vitro and in vivo assays that will be used to address my specific
aims during the ROO phase of this award. In Aims 1 and 2, the major findings were that (i) Th17
show more robust surface expression of E-selectin ligands including glycoCD43 and as a result
adhere more to E-selectin than P-selectin; (ii) that Th17 cells express high levels of the chemokine
receptor 6 (CCR6) and readily increase their adhesion to ICAM-1 and TNF-activated endothelial
monolayers in the presence ofthe CCR6 ligand, CCL20 under physiological shear flow conditions.
Thus Th17 rolling and chemokine activated arrest are important steps during the recruitment to
tissues and my findings open a window to explore the existence of as yet unidentified E-Selectin
ligands that may be exclusively expressed on Th17 cells. This goal is now incorporated into revised
Aims 1 and 2. Similar to what I have done during the K99 award, Aim 3 will interplay with Aims 1
and 2 and will explore using in vivo techniques the relevance of this as yet undefined E-selectin
ligand during Th17 cell recruitment in models of inflammation.
效应T细胞的不同亚群以不同的方式促成各种病理状况。他们的
向组织中的迁移是一个高度调节的过程,涉及T细胞与
血管内皮细胞产生IL-17的T辅助细胞(Th 17),一种新定义的T细胞亚群,
是促炎性的,可以促进器官特异性自身免疫性的炎症病理学,
疾病,以及对某些微生物感染的保护性反应。的总体目标
本项目旨在研究Th 17细胞向炎症部位迁移的调节,
以确定它们归巢到组织中是否能以治疗有用的方式特异性靶向。
根据K99资助期间产生的数据,我的工作假设是Th 17细胞
具有与Th 1细胞不同的迁移表型,Th 1细胞是一种也促进炎症的T细胞类型。我
我已经建立了几个新的体外和体内试验,将用于解决我的具体
在这个奖项的ROO阶段的目标。在目标1和2中,主要发现是(i)Th 17
显示出E-选择素配体(包括glycoCD 43)的更强的表面表达,
与P-选择素相比,粘附更多E-选择素;(ii)Th 17细胞表达高水平趋化因子
受体6(CCR 6),并容易增加其粘附ICAM-1和TNF-活化的内皮细胞
在生理剪切流条件下,CCR 6配体CCL 20存在下的单层。
因此,Th 17滚动和趋化因子激活的停滞是募集过程中的重要步骤,
组织和我的发现打开了一扇窗户,探索尚未确定的E-选择素的存在。
配体,其可以仅在Th 17细胞上表达。这一目标现已纳入经修订的
目标1和2。与我在K99颁奖期间所做的类似,目标3将与目标1相互作用
和2,并将探索使用体内技术的相关性,这尚未确定的E-选择素
在炎症模型中Th 17细胞募集过程中的配体。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Maria Pilar Alcaide Alonso其他文献
Maria Pilar Alcaide Alonso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('Maria Pilar Alcaide Alonso', 18)}}的其他基金
Regulation of T cell immune response in Heart Failure with Preserved Ejection Fraction
保留射血分数对心力衰竭中 T 细胞免疫反应的调节
- 批准号:
10656683 - 财政年份:2023
- 资助金额:
$ 23.7万 - 项目类别:
Mechanisms of T cell activation in cardiac fibrosis and non-ischemic heart failure
心脏纤维化和非缺血性心力衰竭中 T 细胞激活的机制
- 批准号:
10174038 - 财政年份:2019
- 资助金额:
$ 23.7万 - 项目类别:
Mechanisms of T cell activation in cardiac fibrosis and non-ischemic heart failure
心脏纤维化和非缺血性心力衰竭中 T 细胞激活的机制
- 批准号:
10807275 - 财政年份:2019
- 资助金额:
$ 23.7万 - 项目类别:
Mechanisms of T cell activation in cardiac fibrosis and non-ischemic heart failure
心脏纤维化和非缺血性心力衰竭中 T 细胞激活的机制
- 批准号:
10092213 - 财政年份:2019
- 资助金额:
$ 23.7万 - 项目类别:
Mechanisms of T cell activation in cardiac fibrosis and non-ischemic heart failure
心脏纤维化和非缺血性心力衰竭中 T 细胞激活的机制
- 批准号:
10334455 - 财政年份:2019
- 资助金额:
$ 23.7万 - 项目类别:
Mechanisms of T cell activation in cardiac fibrosis and non-ischemic heart failure
心脏纤维化和非缺血性心力衰竭中 T 细胞激活的机制
- 批准号:
10172330 - 财政年份:2019
- 资助金额:
$ 23.7万 - 项目类别:
Mechanisms of T cell activation in cardiac fibrosis and non-ischemic heart failure
心脏纤维化和非缺血性心力衰竭中 T 细胞激活的机制
- 批准号:
10554168 - 财政年份:2019
- 资助金额:
$ 23.7万 - 项目类别:
T Cell mediated immune responses as a regulator of heart failure
T 细胞介导的免疫反应作为心力衰竭的调节剂
- 批准号:
9307971 - 财政年份:2014
- 资助金额:
$ 23.7万 - 项目类别:
T Cell Mediated Immune Responses as a Regulator of Heart Failure
T 细胞介导的免疫反应作为心力衰竭的调节剂
- 批准号:
8750156 - 财政年份:2014
- 资助金额:
$ 23.7万 - 项目类别:
Endothelial regulation of IL17 producing T effector cell migration
内皮调节产生 IL17 的 T 效应细胞迁移
- 批准号:
8307087 - 财政年份:2011
- 资助金额:
$ 23.7万 - 项目类别:
相似海外基金
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y004841/1 - 财政年份:2024
- 资助金额:
$ 23.7万 - 项目类别:
Research Grant
Defining a role for non-canonical mTORC1 activity at focal adhesions
定义非典型 mTORC1 活性在粘着斑中的作用
- 批准号:
BB/Y001427/1 - 财政年份:2024
- 资助金额:
$ 23.7万 - 项目类别:
Research Grant
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y005414/1 - 财政年份:2024
- 资助金额:
$ 23.7万 - 项目类别:
Research Grant
Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.
开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶,以防止术后心脏粘连。
- 批准号:
10669829 - 财政年份:2023
- 资助金额:
$ 23.7万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10587090 - 财政年份:2023
- 资助金额:
$ 23.7万 - 项目类别:
Improving Maternal Outcomes of Cesarean Delivery with the Prevention of Postoperative Adhesions
通过预防术后粘连改善剖宫产的产妇结局
- 批准号:
10821599 - 财政年份:2023
- 资助金额:
$ 23.7万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10841832 - 财政年份:2023
- 资助金额:
$ 23.7万 - 项目类别:
Prevention of Intraabdominal Adhesions via Release of Novel Anti-Inflammatory from Surface Eroding Polymer Solid Barrier
通过从表面侵蚀聚合物固体屏障中释放新型抗炎剂来预防腹内粘连
- 批准号:
10532480 - 财政年份:2022
- 资助金额:
$ 23.7万 - 项目类别:
I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions
I-Corps:一种可喷雾的组织结合水凝胶,可防止术后心脏粘连
- 批准号:
10741261 - 财政年份:2022
- 资助金额:
$ 23.7万 - 项目类别:
Sprayable Polymer Blends for Prevention of Site Specific Surgical Adhesions
用于预防特定部位手术粘连的可喷涂聚合物共混物
- 批准号:
10674894 - 财政年份:2022
- 资助金额:
$ 23.7万 - 项目类别: