Role of SCARF1 in removal of apoptotic debris and protection against autoimmunity
SCARF1 在清除细胞凋亡碎片和防御自身免疫方面的作用
基本信息
- 批准号:10409829
- 负责人:
- 金额:$ 20.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-24 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffinityAmino AcidsApoptoticAutoantibodiesAutoimmune DiseasesAutoimmunityBindingBiochemicalBiological AssayBloodBone MarrowC-terminalCell MaturationCellsChimera organismChromatinChronicClinicalCommunicable DiseasesComplementComplement 1qComplexCysteineCytoplasmic TailDefectDendritic CellsDermatitisDetectionDevelopmentDiseaseElementsEndothelial CellsEpidermal Growth FactorEventExcisionExtracellular DomainFailureGenerationsGoalsHematopoieticHomeostasisImaging TechniquesImmune ToleranceImmune responseImmune systemImmunologyImpairmentIn VitroInflammationIntegral Membrane ProteinLeadLigand BindingLupusMaintenanceMediatingMetabolic DiseasesMolecularMusN-Glycosylation SiteN-terminalNCOA3 geneNatureNephritisPatientsPeptide Signal SequencesPhagocytesPhagocytosisPhosphatidylserinesPhysiologicalPlayPreventionProcessProductionProteinsPublicationsReceptor CellReportingResearchResolutionRoleSignal TransductionSiteSite-Directed MutagenesisSurfaceSystemic Lupus ErythematosusT-Cell ActivationTertiary Protein StructureTestingTissuesWorkacetyl-LDLcell injurychronic inflammatory diseasecytokineglycosylationimmune activationimmune self tolerancein vivolupus-likemacrophagemembernew therapeutic targetpreventprotein protein interactionradioresistantreceptorscavenger receptorsystemic autoimmune diseasetraffickinguptake
项目摘要
Project Summary
Efficient detection and clearance of apoptotic cells is essential in the maintenance of immune
tolerance and tissue homeostasis. Phagocytes are responsible for removal of dying cells;
however, defects in recognition or engulfment of apoptotic cells can lead to chronic inflammation
and autoimmune disease. Accumulation of apoptotic cells in tissues has been associated with the
autoimmune disease systemic lupus erythematosus (SLE), and several receptors on phagocytes
responsible for the clearance of apoptotic debris have been identified. We previously identified
the scavenger receptor expressed on endothelial cells-1 (SCARF1) as the receptor for apoptotic
cells on dendritic cells via interactions with C1q/phosphatidylserine complexes on the dead cells
(Ramirez-Ortiz et.al.; Nature Immunology). Loss of SCARF1 results in impaired uptake of
apoptotic cells in vitro and in vivo, with accumulation of cell corpses in tissues and blood.
Consequently, SCARF1-deficient mice develop lupus-like autoimmune disease. Our previous
findings revealed that SCARF1 is a non-redundant efferocytosis receptor; however, additional
work is needed to identify the mechanisms necessary for SCARF1-mediated removal of apoptotic
cells and prevention of spontaneous autoimmunity in vivo. We hypothesize that SCARF1 plays
an essential role in the physiological clearance of apoptotic debris, and that dysregulated or loss
of SCARF1 expression on phagocytes leads to impaired AC uptake, loss of immune self-tolerance
and development of autoimmunity. We propose to define the domains in SCARF1 that mediate
recognition, signaling and removal of apoptotic cells and determine the relative contribution of
SCARF1 in radioresistant cells vs hematopoietic cells. A comprehensive understanding of all the
processes required for effective apoptotic cell removal can identify new targets not only for Lupus,
but for many autoimmune, metabolic and infectious diseases.
项目摘要
凋亡细胞的有效检测和清除在维持免疫调节中是必不可少的。
耐受性和组织稳态。吞噬细胞负责清除垂死细胞;
然而,识别或吞噬凋亡细胞的缺陷可导致慢性炎症
和自身免疫性疾病。凋亡细胞在组织中的积累与肿瘤的发生有关。
自身免疫性疾病系统性红斑狼疮(SLE)和吞噬细胞上的几种受体
负责清除凋亡碎片。我们之前发现
内皮细胞上表达的清道夫受体-1(SCARF 1)作为细胞凋亡的受体,
通过与死细胞上的C1 q/磷脂酰丝氨酸复合物的相互作用,
(Ramirez-Ortiz等人; Nature Immunology)。SCARF 1的缺失导致
在体外和体内的凋亡细胞,随着组织和血液中细胞尸体的积累。
因此,SCARF 1缺陷小鼠发展成狼疮样自身免疫性疾病。我们以前的
研究结果显示,SCARF 1是一种非冗余的红细胞增多症受体;然而,
需要进行工作来确定SCARF 1介导的细胞凋亡清除所必需的机制,
细胞和预防体内自发性自身免疫。我们假设SCARF 1在
在凋亡碎片的生理清除中起重要作用,
吞噬细胞上SCARF 1表达的降低导致AC摄取受损,免疫自身耐受性丧失,
和自身免疫的发展。我们建议定义SCARF 1中介导
识别,信号传导和去除凋亡细胞,并确定相对贡献
抗辐射细胞与造血细胞中的SCARF 1。全面了解所有
有效去除凋亡细胞所需的过程不仅可以鉴定狼疮的新靶点,
但对于许多自身免疫性、代谢性和感染性疾病也是如此。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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Zaida Gisela Ramirez-Ortiz其他文献
Zaida Gisela Ramirez-Ortiz的其他文献
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{{ truncateString('Zaida Gisela Ramirez-Ortiz', 18)}}的其他基金
Role of SCARF1 in removal of apoptotic debris and protection against autoimmunity
SCARF1 在清除细胞凋亡碎片和防御自身免疫方面的作用
- 批准号:
10288804 - 财政年份:2021
- 资助金额:
$ 20.94万 - 项目类别:
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