Functional insights into the IRF5 genetic variants marking SLE risk.
对标记 SLE 风险的 IRF5 遗传变异的功能见解。
基本信息
- 批准号:9116776
- 负责人:
- 金额:$ 19.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-08-01 至 2018-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdrenal Cortex HormonesAmino AcidsAutoimmune DiseasesAutoimmunityBiochemicalBiologicalCellsDataDendritic CellsDevelopmentExonsFamilyGenderGenesGeneticGenetic PolymorphismGlutamic AcidGoalsHaplotypesHealthImmuneIndividualInterferon ActivationInterferon Type IInterferonsLupusMolecularMolecular ConformationPatientsPharmaceutical PreparationsPredispositionProductionProlineRNA SplicingRaceRegulationResearchResearch ProposalsRiskRoleSerineSignal PathwaySignal TransductionSystemic Lupus ErythematosusThreonineTranslatingVariantbasedrug developmentgene inductiongenetic associationgenetic variantgenome wide association studyhigh riskimmune activationinsertion/deletion mutationinsightprotein functionrisk varianttranscription factor
项目摘要
DESCRIPTION (provided by applicant): The goal of the proposed research is to determine how the interferon regulatory factor 5(IRF5) lupus risk variant translates into biological risk of systemic lupus erythematosus (SLE). Genome wide association studies (GWAS) have identified IRF5 as one of the most strongly associated genes with susceptibility to SLE. Although the genetic association of IRF5 with lupus is clear, the exact mechanism by which IRF5 risk variant promotes susceptibility for lupus is still unknown. We hypothesize that IRF8 could be a negative regulatory factor of IRF5 activity under normal conditions, while in lupus the IRF5 exon 6 risk variants are capable of escaping this negative regulation thereby activating type I IFNs leading to aberrant immune activation. To address this question, we will (SA1) characterize IRF5 exon 6 variants in pDCs using molecular and biochemical approaches, (SA2) investigate the effects of IRF8 on IRF5 exon 6 variants, and (SA3) effect of IRF5 exon 6 variation on IRF5 activation in SLE patients. If IRF8 blocks IRF5 activation, this will be a significant step to gain the mechanistic understanding of aberrant production type I IFNs and immune activation in lupus.
描述(由申请人提供):拟议研究的目标是确定干扰素调节因子5(IRF5)狼疮风险变体如何转化为系统性红斑狼疮(SLE)的生物风险。全基因组关联研究(GWAS)已经确定IRF5是与SLE易感性最强相关的基因之一。虽然IRF5与狼疮的遗传关联是明确的,但IRF5风险变体促进狼疮易感性的确切机制仍然未知。我们假设IRF8在正常情况下可能是IRF5活性的负调节因子,而在狼疮中IRF5外显子6风险变体能够逃避这种负调节,从而激活I型IFN,导致异常免疫激活。为了解决这个问题,我们将(SA1)使用分子和生物化学方法表征pDC中的IRF 5外显子6变体,(SA2)研究IRF 8对IRF 5外显子6变体的影响,以及(SA3)SLE患者中IRF 5外显子6变体对IRF 5激活的影响。如果IRF8阻断IRF5活化,这将是获得对狼疮中I型IFN异常产生和免疫活化的机制理解的重要一步。
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)
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Ram Savan其他文献
Ram Savan的其他文献
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{{ truncateString('Ram Savan', 18)}}的其他基金
The splicing factor CELF2 suppresses RNA ligands sensed by RIG-I-like receptor
剪接因子CELF2抑制RIG-I样受体感知的RNA配体
- 批准号:
10654469 - 财政年份:2023
- 资助金额:
$ 19.72万 - 项目类别:
Regulation of cardiomyocyte inflammation during viral infection
病毒感染过程中心肌细胞炎症的调节
- 批准号:
10244888 - 财政年份:2020
- 资助金额:
$ 19.72万 - 项目类别:
Regulation of cardiomyocyte inflammation during viral infection
病毒感染过程中心肌细胞炎症的调节
- 批准号:
9894164 - 财政年份:2020
- 资助金额:
$ 19.72万 - 项目类别:
Translational Reprogramming by Regulatory T Cells
调节性 T 细胞的翻译重编程
- 批准号:
9765776 - 财政年份:2019
- 资助金额:
$ 19.72万 - 项目类别:
Functional insights into the IRF5 genetic variants marking SLE risk.
对标记 SLE 风险的 IRF5 遗传变异的功能见解。
- 批准号:
8968765 - 财政年份:2015
- 资助金额:
$ 19.72万 - 项目类别:
Novel regulatory mechanisms control IFNL3 expression during HCV infection
HCV 感染过程中控制 IFNL3 表达的新调控机制
- 批准号:
8990447 - 财政年份:2014
- 资助金额:
$ 19.72万 - 项目类别:
Novel regulatory mechanisms control IFNL3 expression during HCV infection
HCV 感染过程中控制 IFNL3 表达的新调控机制
- 批准号:
8611757 - 财政年份:2014
- 资助金额:
$ 19.72万 - 项目类别:
Novel regulatory mechanisms control IFNL3 expression during HCV infection
HCV 感染过程中控制 IFNL3 表达的新调控机制
- 批准号:
9273703 - 财政年份:2014
- 资助金额:
$ 19.72万 - 项目类别: