CXCL16/CXCR6 and Their Roles in Autoimmune Arthritis
CXCL16/CXCR6 及其在自身免疫性关节炎中的作用
基本信息
- 批准号:7451534
- 负责人:
- 金额:$ 2.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-01 至 2008-12-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAnimal ModelAnti-Inflammatory AgentsAntigen-Presenting CellsArthritisAutoimmune DiseasesB cell differentiationB-LymphocytesCCR5 geneCX3CL1 geneCXCR3 geneCXCR6 geneCell AdhesionCellsChemokine, OtherChimeric ProteinsChronicCollagen ArthritisComparative StudyDevelopmentDiseaseDown-RegulationEtiologyEventExperimental ModelsFamilyFractalkineGoalsHomingHumanImmigrationImmune responseInflammationInflammatoryInflammatory ResponseInvestigationJointsKineticsLeukocyte TraffickingLeukocytesLigandsLymphocyteLymphocyte FunctionLymphoidLymphoid TissueMaintenanceMediatingMembraneMolecularMucinsMusPathogenesisPathway interactionsPatientsPatternPlayPositioning AttributePreventionProcessProductionProteinsRegulationResearch PersonnelRheumatoid ArthritisRoleSeveritiesSignal TransductionSiteStagingStructureSynovial FluidSynovial MembraneT-Cell ActivationT-LymphocyteTh1 CellsTherapeutic InterventionTissuesTransmembrane DomainUp-RegulationWorkautoimmune arthritiscell motilitycell typechemokinecytokinedesignimmune functioninsightlymph nodesmacrophagemembernovelprogramsreceptorresponsetraffickingtranscription factor
项目摘要
The etiology and pathogenesis of rheumatoid arthritis (RA) remain obscure despite intense
investigation. Chemokines play a critical role in attracting and retaining leukocytes in the inflamed joints.
However, the precise mechanism for cell positioning in the joints is unclear.
The long-term goal of this project is to understand the mechanism of cell trafficking and inflammatory
responses in nonlymphoid tissues in the settings of autoimmune diseases. Recently we have found that
CXCL16, a newly identified chemokine, and its receptor, CXCR6, are highly expressed in the joints of mice
with collagen-induced arthritis (CIA), an animal model of RA. CXCL16 is the second member of the
chemokine family with a transmembrane domain. The receptor-bearing cells are mainly Th1 cells, display
extralymphoid tissue homing potential and are enriched in inflamed synovial fluid of RA patients. Treatment
of mice with CXCL16-lg fusion protein significantly ameliorates CIA. Thus, we hypothesize that
CXCL16/CXCR6 play an important role in the pathogenesis of autoimmune arthritis. This project will focus
on the mechanisms that regulate CXCL16/CXCR6 expression and the contribution of CXCL16/CXCR6 to
the initiation and progression of CIA. Chemokines that are preferentially expressed in Th1-mediated
inflammatory disorders like RA, such as CXCR3 and CCR5, will also be investigated during the course of
CIA as comparative studies to further elucidate the role of CXCL16/CXCR6 in the pathogenesis of CIA. In
addition, we hypothesize that CXCL16/CXCR6 may mediate interactions among T cell, B cells,
macrophages and other cells in the affected sites because of the unique structure CXCL16 as a membrane
chemokine and its expression pattern. The role of CXCL16/CXCR6 in mediating T cell-antigen presenting
cells will be studied. Aside from enhancing our understanding of leukocyte migration in rheumatoid joints,
these studies are expected to provide important information regarding chemokine functions in regulating
activation and differentiation of lymphocytes and macrophages during inflammatory responses. The study
will also provide insights into new targets for designing anti-inflammatory agents in autoimmune arthritis and
other autoimmune diseases.
尽管类风湿性关节炎(RA)的病因和发病机制非常复杂,但其病因和发病机制仍然不清楚。
调查。趋化因子在吸引和保留发炎关节中的白细胞方面发挥着关键作用。
然而,细胞在关节中定位的精确机制尚不清楚。
该项目的长期目标是了解细胞运输和炎症的机制
自身免疫性疾病中非淋巴组织的反应。最近我们发现
CXCL16是一种新发现的趋化因子,其受体CXCR6在小鼠关节中高表达
胶原诱导的关节炎(CIA),一种 RA 动物模型。 CXCL16是第二个成员
具有跨膜结构域的趋化因子家族。受体承载细胞主要是Th1细胞,显示
淋巴外组织归巢潜力,并且在 RA 患者发炎的滑液中富含。治疗
具有 CXCL16-Ig 融合蛋白的小鼠的 CIA 显着改善。因此,我们假设
CXCL16/CXCR6在自身免疫性关节炎的发病机制中发挥重要作用。该项目将重点
关于调节 CXCL16/CXCR6 表达的机制以及 CXCL16/CXCR6 对
中央情报局的发起和发展。优先在 Th1 介导下表达的趋化因子
RA 等炎症性疾病,如 CXCR3 和 CCR5,也将在治疗过程中进行研究
CIA作为对比研究,进一步阐明CXCL16/CXCR6在CIA发病机制中的作用。在
此外,我们假设 CXCL16/CXCR6 可能介导 T 细胞、B 细胞、
由于CXCL16作为膜的独特结构,受影响部位的巨噬细胞和其他细胞
趋化因子及其表达模式。 CXCL16/CXCR6 在介导 T 细胞抗原呈递中的作用
细胞将被研究。除了增强我们对类风湿关节中白细胞迁移的了解之外,
这些研究有望提供有关趋化因子调节功能的重要信息
炎症反应期间淋巴细胞和巨噬细胞的激活和分化。研究
还将为设计自身免疫性关节炎抗炎药物的新靶点提供见解
其他自身免疫性疾病。
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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{{ truncateString('SHUHUA HAN', 18)}}的其他基金
CXCL16/CXCR6 and Their Roles in Autoimmune Arthritis
CXCL16/CXCR6 及其在自身免疫性关节炎中的作用
- 批准号:
8132742 - 财政年份:2010
- 资助金额:
$ 2.75万 - 项目类别:
CXCL16 as a therapeutic target for atherosclerosis
CXCL16作为动脉粥样硬化的治疗靶点
- 批准号:
7876814 - 财政年份:2009
- 资助金额:
$ 2.75万 - 项目类别:
CXCL16 as a therapeutic target for atherosclerosis
CXCL16作为动脉粥样硬化的治疗靶点
- 批准号:
7744566 - 财政年份:2009
- 资助金额:
$ 2.75万 - 项目类别:
CXCL16/CXCR6 and Their Roles in Autoimmune Arthritis
CXCL16/CXCR6 及其在自身免疫性关节炎中的作用
- 批准号:
7335584 - 财政年份:2005
- 资助金额:
$ 2.75万 - 项目类别:
CXCL16/CXCR6 and Their Roles in Autoimmune Arthritis
CXCL16/CXCR6 及其在自身免疫性关节炎中的作用
- 批准号:
7161337 - 财政年份:2005
- 资助金额:
$ 2.75万 - 项目类别:
CXCL16/CXCR6 and Their Roles in Autoimmune Arthritis
CXCL16/CXCR6 及其在自身免疫性关节炎中的作用
- 批准号:
7030944 - 财政年份:2005
- 资助金额:
$ 2.75万 - 项目类别:
CXCL16/CXCR6 and Their Roles in Autoimmune Arthritis
CXCL16/CXCR6 及其在自身免疫性关节炎中的作用
- 批准号:
6920904 - 财政年份:2005
- 资助金额:
$ 2.75万 - 项目类别:
CXCL 16/CXCR6 and Their Roles in Autoimmune Arthritis
CXCL 16/CXCR6 及其在自身免疫性关节炎中的作用
- 批准号:
6775372 - 财政年份:2004
- 资助金额:
$ 2.75万 - 项目类别:
Regulation of the B-Cell Development and Differentiation
B 细胞发育和分化的调节
- 批准号:
6760098 - 财政年份:2003
- 资助金额:
$ 2.75万 - 项目类别:
Regulation of the B-Cell Development and Differentiation
B 细胞发育和分化的调节
- 批准号:
6682636 - 财政年份:2003
- 资助金额:
$ 2.75万 - 项目类别:
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