Immune Checkpoints in Acute Respiratory Distress Syndrome (IC-ARDS)
急性呼吸窘迫综合征 (IC-ARDS) 中的免疫检查点
基本信息
- 批准号:10655533
- 负责人:
- 金额:$ 54.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-05 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:Acute Respiratory Distress SyndromeAffectAlveolarAlveolar MacrophagesAnti-Inflammatory AgentsAntigensBilateralBindingBiologicalBiological MarkersBronchoscopyCell membraneCell physiologyCell surfaceCellsCentrifugationCessation of lifeClinicalClinical TrialsCluster AnalysisComplicationCritical IllnessCytometryDataDefectEnrollmentFrightFunctional disorderHeterogeneityHypoxemiaIL17 geneIL8 geneImmuneImmune checkpoint inhibitorImmune responseImmunosuppressionImpairmentInfiltrationInflammationInflammatoryInjuryIntensive Care UnitsInterferon Type IIInterleukin-6KnowledgeLeadLeukocytesLigandsLinkLiquid substanceLungMacrophageMeasurementMeasuresMechanical ventilationMediatingMedicalMedical centerModelingMolecularMorbidity - disease rateMusNatureOperative Surgical ProceduresOutcomePathogenicityPathway interactionsPatientsPharmacologic SubstancePhenotypePlasmaPlayProductionProliferatingProteinsProteomicsPulmonary InflammationRNA SplicingReceptor SignalingRegulatory T-LymphocyteResolutionRespiratory FailureRiskRisk FactorsRoleSepsisSeveritiesSeverity of illnessSignal TransductionStainsStudy SubjectSubgroupSurfaceSyndromeT cell regulationT cell responseT-Cell ProliferationT-Cell ReceptorT-LymphocyteT-Lymphocyte SubsetsThoracic RadiographyTissuesTraumaUnited StatesValidationVariantVentilatorcirculating biomarkerscohortcostcytokinedifferential expressiondisabilityexperiencehigh dimensionalityhigh riskimmune checkpointimmune functionimmunoregulationinhibitorlung injurymicrovesiclesmonocytemortalitymortality risknovelparticipant enrollmentpatient subsetsperipheral bloodpersonalized approachprognosticationprogrammed cell death ligand 1programmed cell death protein 1protein expressionreceptorrecruitresponseside effecttissue injuryventilationvesicular release
项目摘要
PROJECT SUMMARY/ABSTRACT
Acute respiratory distress syndrome (ARDS) is an important cause of morbidity and mortality resulting in over
74,000 intensive care unit deaths per year in the United States. Patients often present with rapidly progressive
respiratory failure requiring prolonged mechanical ventilation which is costly and associated with long term
disability. A more refined understanding of the pathophysiologic mechanisms of ARDS may guide more
personalized approaches for prognostication and therapy. The immune “checkpoint” pathway includes the
receptor Programmed cell death protein 1 (PD-1) and its ligand Programmed death-ligand 1 (PD-L1). The
binding of PD-L1 to PD-1 leads to negative regulation of T cell receptor signaling. PD-1 and PD-L1 have been
associated with defects in immune function in patients with sepsis which is a major risk factor for ARDS. For
example, high PD-1 expression on circulating T cells in patients with sepsis is associated with decreased T cell
interferon-gamma production. However, other studies suggest a role for this pathway in limiting tissue
inflammation. Preliminary data in this proposal shows that patients with ARDS who have prolonged mechanical
ventilation have lower expression of PD-L1 on alveolar macrophages. Further, a serious side effect of
pharmaceutical inhibitors of this pathway termed “checkpoint inhibitors” is immune mediated tissue injury such
as an ARDS-like pneumonitis. Thus the role of this pathway in modulating immune responses may be critical to
our understanding of ARDS. The hypothesis of this study is that immune checkpoint proteins are protective
against poor outcomes in ARDS by limiting tissue injury. This study will also investigate potential mechanisms
of this association through promotion of regulatory T cell responses or limiting inflammatory T cell responses.
Study subjects will be enrolled into a discovery cohort where measurements will be performed using novel high
dimensional mass cytometry to identify expression of these proteins on a single cell basis. A validation cohort
will be recruited externally to confirm these findings. Aim 1 will identify whether cell surface immune checkpoint
protein expression is associated with severity of ARDS, Aim 2 will focus on mechanisms behind the
association in modulating T cell responses, and Aim 3 will identify potential soluble measures of this pathway.
This study aims to identify a biologically relevant immune signature of patients at risk for prolonged mechanical
ventilation and death from ARDS.
项目总结/文摘
项目成果
期刊论文数量(0)
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Carmen R Mikacenic其他文献
Carmen R Mikacenic的其他文献
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{{ truncateString('Carmen R Mikacenic', 18)}}的其他基金
Systems Immunology profiling of respiratory viral infections in vulnerable populations
易感人群呼吸道病毒感染的系统免疫学分析
- 批准号:
10420949 - 财政年份:2022
- 资助金额:
$ 54.26万 - 项目类别:
Systems Immunology profiling of respiratory viral infections in vulnerable populations
易感人群呼吸道病毒感染的系统免疫学分析
- 批准号:
10598132 - 财政年份:2022
- 资助金额:
$ 54.26万 - 项目类别:
Immune Checkpoints in Acute Respiratory Distress Syndrome (IC-ARDS)
急性呼吸窘迫综合征 (IC-ARDS) 中的免疫检查点
- 批准号:
10254220 - 财政年份:2020
- 资助金额:
$ 54.26万 - 项目类别:
Immune Checkpoints in Acute Respiratory Distress Syndrome (IC-ARDS)
急性呼吸窘迫综合征 (IC-ARDS) 中的免疫检查点
- 批准号:
10434143 - 财政年份:2020
- 资助金额:
$ 54.26万 - 项目类别:
Influence of TLR1 Polymorphisms on T-Regulatory Cells in ARDS
TLR1 多态性对 ARDS 调节性 T 细胞的影响
- 批准号:
8865672 - 财政年份:2014
- 资助金额:
$ 54.26万 - 项目类别:
Influence of TLR1 Polymorphisms on T-Regulatory Cells in ARDS
TLR1 多态性对 ARDS 调节性 T 细胞的影响
- 批准号:
8616243 - 财政年份:2014
- 资助金额:
$ 54.26万 - 项目类别:
Influence of TLR1 Polymorphisms on T-Regulatory Cells in ARDS
TLR1 多态性对 ARDS 调节性 T 细胞的影响
- 批准号:
9271218 - 财政年份:2014
- 资助金额:
$ 54.26万 - 项目类别:
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