Immune-Metabolic Regulation of Biliary Atresia
胆道闭锁的免疫代谢调节
基本信息
- 批准号:10645435
- 负责人:
- 金额:$ 11.66万
- 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:2023-04-15 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:2 year oldATAC-seqAnti-Inflammatory AgentsApoptoticAreaArginineBile fluidBiliaryBiliary AtresiaBiochemical PathwayBiological AssayBiologyCellsCharacteristicsChildhoodCholestasisChromatinClinicalCollaborationsCritical PathwaysDataDiagnosisDiseaseDrainage procedureEarly identificationEpigenetic ProcessFoundationsFreezingFutureGene ExpressionGene Expression ProfileGene Expression RegulationGenesGenetic TranscriptionGranulocyte-Macrophage Colony-Stimulating FactorHepaticHepatocyteHumanImmuneImmune responseInfantInflammatoryLiverMacrophageMeasuresMedicalMentorsMetabolicMetabolismModificationMusNatureNitric Oxide SynthaseObstructionOperative Surgical ProceduresOutcomePathogenesisPathway interactionsPatient-Focused OutcomesPatientsPhenotypePolyaminesPredictive ValuePrognostic MarkerPutrescineROC CurveRegulationResearchResearch PersonnelRheumatologyRoleRunningSamplingSerumSpermidineSpermineSurvival RateTimeTransplantationTransposaseUp-RegulationValidationcell dedifferentiationcohortdifferential expressionepigenetic regulationhydrophilicityimmunoregulationinfancyinnovationliver transplantationmetabolomicsmonocytenew therapeutic targetnovelprognosticprogramsrecruitsingle nucleus RNA-sequencingsurvival predictiontotal measurement Bilirubintranscriptional reprogrammingtreatment strategyuptake
项目摘要
Biliary atresia (BA) is a cholestatic liver disease of infancy and is the leading cause of pediatric
liver transplantation. Current evidence supports the principle that BA arises from an aberrant
immune response to an environmental trigger. However, the exact mechanism of disease remains
unknown. While macrophages (M) have been implicated in both human and murine BA, M are
heterogeneous by nature and the metabolic networks responsible for pro-restorative vs pro-
inflammatory M polarization have not been defined. Our central premise is that identifying
macrophage-specific immune-metabolic signatures associated with patient outcome will lead to
novel prognostic biomarkers and cell-subset specific therapies to prolong transplant-free survival.
We have been the first to identify a prognostic metabolite signature in BA infants at the time of
diagnosis. We have shown that distinct changes in serum arginine metabolites, particularly
increased polyamines, in BA infants at the time of diagnosis was associated with increased
survival with native liver (SNL) at the age of 2 years despite no baseline differences in clinical
characteristics. Polyamines are known to reprogram M to an anti-inflammatory phenotype, in
part through efferocytosis (i.e. apoptotic cell uptake). Our preliminary data found that BA patients
with a polyamine-high metabolic signature had increased hepatic numbers of previously
characterized monocyte-like M (MLM, increased expression for genes associated with
monocytes) and serum GM-CSF. We thereby hypothesize that recruited MLM promote hepatic
adaptation to biliary obstruction; thus, metabolic and epigenetic reprogramming of MLM towards
and anti-inflammatory phenotype will be associated with SNL at 2 years of age. To investigate
this hypothesis, we will: 1) define the prognostic role for serum arginine metabolites, and 2)
identify cell subset specific transcriptional phenotypes associated with SNL.
胆道闭锁(BA)是一种婴儿期胆汁淤积性肝脏疾病,是儿童胆汁淤积性肝脏疾病的主要原因
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Sarah Ann Taylor其他文献
A Systematic Review and Comprehensive Discussion of Social Validity Measurement in Behavioural Intervention for Paediatric Feeding Disorders
- DOI:
10.1007/s10566-024-09812-w - 发表时间:
2024-06-27 - 期刊:
- 影响因子:1.600
- 作者:
Tessa Taylor;Laura E. Phipps;Kathryn M. Peterson;Sarah Ann Taylor - 通讯作者:
Sarah Ann Taylor
Sarah Ann Taylor的其他文献
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{{ truncateString('Sarah Ann Taylor', 18)}}的其他基金
Macrophage Regulation of Immune Pathogenesis of Biliary Atresia
巨噬细胞对胆道闭锁免疫发病机制的调节
- 批准号:
10543779 - 财政年份:2021
- 资助金额:
$ 11.66万 - 项目类别:
Macrophage Regulation of Immune Pathogenesis of Biliary Atresia
巨噬细胞对胆道闭锁免疫发病机制的调节
- 批准号:
10761123 - 财政年份:2021
- 资助金额:
$ 11.66万 - 项目类别:
Macrophage Regulation of Immune Pathogenesis of Biliary Atresia
巨噬细胞对胆道闭锁免疫发病机制的调节
- 批准号:
10320943 - 财政年份:2021
- 资助金额:
$ 11.66万 - 项目类别:
Immune Modulation of Macrophages in Obstructive Cholestasis
巨噬细胞在阻塞性胆汁淤积中的免疫调节
- 批准号:
10040905 - 财政年份:2020
- 资助金额:
$ 11.66万 - 项目类别:
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