Immune Mechanisms of Alloinjury
Immune Mechanisms of Alloinjury
批准号:
9022509
负责人:
JOHN A BELPERIO
金额:
$44.8万
依托单位国家:
美国
项目类别:
财政年份:
2012
资助国家:
美国
项目状态:
已结题
起止时间:
2012-05-15 至 2017-02-28
关键词:
AcuteAlloantigenAllograftingAnimalsAntigen-Presenting CellsBiologicalBiologyBronchiolitisBronchiolitis ObliteransCCL17 geneCCL22 geneCD4 Positive T LymphocytesCD8B1 geneCellsChronicClinicalClinical TrialsDataDevelopmentFunctional disorderFutureGoalsHelper-Inducer T-LymphocyteHomingHumanHuman BiologyImmuneInflammatoryLeadLicensingLigandsLung TransplantationLymphoid TissueMaintenanceMediatingMemoryModelingMusNatureObservational StudyPathogenesisPatientsPharmacologic SubstancePopulationProcessPrognostic MarkerRisk FactorsRoleSecondary toSyndromeT-LymphocyteTestingTherapeutic TrialsTranslatingTransplant RecipientsViral Tumor Antigensallograft rejectionarmbaseimprovedinsightlung allograftnovelpre-clinicalpreventprospectiveresponsetranslational study
中文摘要
描述(申请人提供):慢性肺移植排斥反应,也称为闭塞性细支气管炎综合征(BOS),是一种炎症过程,最终导致移植肺的纤维闭塞;然而,涉及的确切机制(S)尚不清楚。我们的初步数据表明,CCR4/配体(CCL17和CCL22)的相互作用对同种异体移植排斥反应的传入和传出臂都很重要。具体而言,CCR4/配体
同种异体反应性传入臂中的生物轴通过促进:1)原始的CD4和CD8 T细胞归巢到次级淋巴组织,以及2)CD4辅助T细胞和抗原提呈细胞(APC)之间的结内相互作用,从而允许APC产生同种异体特异性CD8 T细胞,来协调同种异体致敏作用。同种异体反应性传出臂中的CCR4/配体生物轴促进:1)CD4辅助T细胞维持CD8记忆细胞的克隆性群体,并促进同种异体特异性CD8T细胞向移植物的募集,最终导致慢性肺移植物功能障碍。这一提议产生的发现将成为未来药物试验的基础,这些药物可以抑制CCR4/配体的相互作用,目的是预防/治疗肺移植后的BOS。
英文摘要
DESCRIPTION (provided by applicant): Chronic lung allograft rejection, also known as bronchiolitis obliterans syndrome (BOS), is an inflammatory process that ends in fibro-obliteration of the allograft airways; however the exact mechanism(s) involved are unknown. Our preliminary data demonstrates that CCR4/ligands (CCL17 and CCL22) interaction is important for both the afferent and efferent arms of allograft rejection. Specifically, CCR4/ligand
biological axis in the afferent arm of alloreactivity orchestrates allosensitization by promoting: 1) the homing of naïve CD4 and CD8 T cells to secondary lymphoid tissues and 2) the intranodal interactions between CD4 helper T cell and antigen presenting cells (APC) which licenses the APC to generate allospecific CD8 T cells. The CCR4/ligand biological axis in the efferent arm of alloreactivity promotes: 1) CD4 helper T cells to maintain clonal populations of CD8 memory cells and enhances the recruitment of allospecific CD8 T cells to the allograft that eventually leads to chronic lung allograft dysfunction. Discoveries generated by this proposal will be the basis for future therapeutic trials of pharmaceutical agents that inhibit CCR4/ligands interaction with the goal of preventing/treating BOS post-lung transplantation.
期刊论文(6)
专著(0)
科研奖励(0)
会议论文
Preoperative cardiac variables of diastolic dysfunction and clinical outcomes in lung transplant recipients.
肺移植受者舒张功能障碍的术前心脏变量和临床结果。
DOI:
10.1155/2013/391620
发表时间:
2013
期刊:
Journal of transplantation
影响因子:
2.5
作者:
[Yadlapati,Ajay, Lynch3rd,JosephP, Saggar,Rajan, Ross,David, Belperio,JohnA, Weigt,Stephen, Ardehali,Abbas, Grogan,Tristan, Yang,EricH, Aboulhosn,Jamil]
通讯作者:
Aboulhosn,Jamil
DOI:
10.1055/s-0033-1348467
发表时间:
2013-06
期刊:
Seminars in respiratory and critical care medicine
影响因子:
3.2
作者:
[Weigt SS, DerHovanessian A, Wallace WD, Lynch JP 3rd, Belperio JA]
通讯作者:
Belperio JA
Lung Transplant Clinical Trial Network (LT-CTN)
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批准号:10469461
-
项目类别:
-
资助金额:$297.54万
-
财政年份:2021
-
负责人:JOHN A BELPERIO
-
依托单位:
Lung Transplant Clinical Trial Network (LT-CTN)
-
批准号:10636959
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项目类别:
-
资助金额:$297.4万
-
财政年份:2021
-
负责人:JOHN A BELPERIO
-
依托单位:
Validation of an in vitro model of progressive fibrosis that mimics Idiopathic Pulmonary Fibrosis
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批准号:10027230
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项目类别:
-
资助金额:$48.84万
-
财政年份:2021
-
负责人:JOHN A BELPERIO
-
依托单位:
Validation of an in vitro model of progressive fibrosis that mimics Idiopathic Pulmonary Fibrosis
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批准号:10350549
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项目类别:
-
资助金额:$63.04万
-
财政年份:2021
-
负责人:JOHN A BELPERIO
-
依托单位:
Lung Transplant Clinical Trial Network (LT-CTN)
-
批准号:10282197
-
项目类别:
-
资助金额:$298.12万
-
财政年份:2021
-
负责人:JOHN A BELPERIO
-
依托单位:
Validation of an in vitro model of progressive fibrosis that mimics Idiopathic Pulmonary Fibrosis
-
批准号:10542830
-
项目类别:
-
资助金额:$63.04万
-
财政年份:2021
-
负责人:JOHN A BELPERIO
-
依托单位:
Epithelial Progenitor Cell Dysfunction in the Fibroproliferative Process of CLAD
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批准号:10198013
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项目类别:
-
资助金额:$46.8万
-
财政年份:2012
-
负责人:JOHN A BELPERIO
-
依托单位:
Epithelial Progenitor Cell Dysfunction in the Fibroproliferative Process of CLAD
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批准号:10450043
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项目类别:
-
资助金额:$46.8万
-
财政年份:2012
-
负责人:JOHN A BELPERIO
-
依托单位:
Immune Mechanisms of Alloinjury
-
批准号:8617295
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项目类别:
-
资助金额:$43.9万
-
财政年份:2012
-
负责人:JOHN A BELPERIO
-
依托单位:
Immune Mechanisms of Alloinjury
-
批准号:8810687
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项目类别:
-
资助金额:$44.12万
-
财政年份:2012
-
负责人:JOHN A BELPERIO
-
依托单位:
Immune Mechanisms of Alloinjury
-
批准号:8469899
-
项目类别:
-
资助金额:$42.65万
-
财政年份:2012
-
负责人:JOHN A BELPERIO
-
依托单位:
Immune Mechanisms of Alloinjury
-
批准号:8272475
-
项目类别:
-
资助金额:$44.8万
-
财政年份:2012
-
负责人:JOHN A BELPERIO
-
依托单位:
The Role of Chemokines During Lung Allograft Dysfunction
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批准号:7842039
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项目类别:
-
资助金额:$28.85万
-
财政年份:2009
-
负责人:JOHN A BELPERIO
-
依托单位:
The Role of Chemokines During Lung Allograft Dysfunction
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批准号:6904303
-
项目类别:
-
资助金额:$34.76万
-
财政年份:2005
-
负责人:JOHN A BELPERIO
-
依托单位:
The Role of Chemokines During Lung Allograft Dysfunction
-
批准号:7467357
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项目类别:
-
资助金额:$32.96万
-
财政年份:2005
-
负责人:JOHN A BELPERIO
-
依托单位:
The Role of Chemokines During Lung Allograft Dysfunction
-
批准号:7647383
-
项目类别:
-
资助金额:$32.96万
-
财政年份:2005
-
负责人:JOHN A BELPERIO
-
依托单位:
The Role of Chemokines During Lung Allograft Dysfunction
-
批准号:7265285
-
项目类别:
-
资助金额:$32.96万
-
财政年份:2005
-
负责人:JOHN A BELPERIO
-
依托单位:
UCLA IPF Clinical Research Network
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批准号:7616765
-
项目类别:
-
资助金额:$19.7万
-
财政年份:2005
-
负责人:JOHN A BELPERIO
-
依托单位:
The Role of Chemokines During Lung Allograft Dysfunction
-
批准号:7102672
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项目类别:
-
资助金额:$33.95万
-
财政年份:2005
-
负责人:JOHN A BELPERIO
-
依托单位:
CHEMOKINE BIOLOGY IN BRONCHIOLITIS OBLITERANS SYNDROME
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批准号:6530600
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项目类别:
-
资助金额:$12.18万
-
财政年份:2001
-
负责人:JOHN A BELPERIO
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依托单位:
海外基金