Lymphoid neogenesis and CD4+T cell differentiation in primary Sjogren's syndrome
原发性干燥综合征中的淋巴新生和 CD4 T 细胞分化
基本信息
- 批准号:7687681
- 负责人:
- 金额:$ 25.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-05-01 至 2014-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAntigen PresentationAntinuclear AntibodiesArchivesAutoantibodiesAutoimmune DiseasesAutoimmunityB-LymphocytesBiopsyBoxingCD4 Positive T LymphocytesCD4/CD8 ratio procedureCD8B1 geneCell Differentiation processCellsCharacteristicsChronicDefectDendritic CellsDevelopmentDiagnosisDiseaseEffector CellEnvironmentEpitopesEquilibriumFigs - dietaryFollicular Dendritic CellsFrequenciesFresh TissueGene ExpressionGenerationsHelper-Inducer T-LymphocyteHigh Endothelial VenuleHomingIL2RA geneImmuneImmune ToleranceImmune responseImmunityInfiltrationInflammationInflammatoryInjuryInterleukin-1Interleukin-10Interleukin-17Interleukin-4Interleukin-6Lacrimal gland structureLeadLigandsLightLinkLocationLymphatic vesselLymphocyteLymphoidLymphoid TissueMeasuresMediatingMemoryMessenger RNAMethodsMinorMinor salivary gland structureOrganPaperPathogenesisPathologicPatientsPhenotypePopulationProcessProductionRecruitment ActivityRegulationReportingRoleSalivarySalivary GlandsSecondary toSiteSjogren&aposs SyndromeSpleenStructure of germinal center of lymph nodeStudy modelsSurrogate MarkersSyndromeT memory cellT-LymphocyteTALL-1 proteinTh1 CellsTh2 CellsThymus GlandTissuesTumor Necrosis Factor-BetaTumor Necrosis Factor-alphaTumor Necrosis FactorsXerophthalmiaXerostomiabasecell typechemokinecohortcytokineeye drynessinterestinterleukin-23lymph nodesmemory CD4 T lymphocytemigrationperipheral bloodreceptor
项目摘要
Primary Sjogren's syndrome (pSS) is a systemic chronic inflammatory autoimmune disease characterized by
dry eyes and dry mouth. Essential histopathologic features of pSS include focal infiltrations of T and B cells
in the salivary and lacrimal glands that lead to tissue injury and chronic inflammation. In some cases, the
histopathologic changes develop into tertiary lymphoid tissues or organs (TLs) via a process called lymphoid
neogenesis. TLOs resemble spleen and lymph nodes in their cellular composition and organization. TLOs
may serve as a place where recruitment of T cells with lymphoid homing capacity (naive and central memory
cells) as well as their activation, proliferation and differentiation occur. CD4+ T cells that orchestrate immune
responses can be divided into T-helper (Th)1, Th2 and Th17 cells as well as CD4+ T cells with regulatory
function including forkhead box P3 (FOXP3)-positive regulatory T cells (Treg). Although T cells and their
cytokines are found in the salivary tissues of pSS, it is unknown which type of T cells has a leading role in
the pathogenesis. This project investigates the hypothesis that patients with pSS have an altered balance of
Th17 and Treg immune responses that is caused by chronic inflammation with lymphoid neogenesis and
defect(s) in differentiating and functioning of Th17 cells and Treg based on the facts that Th17 cells potently
induce inflammation while Treg suppress it. Plus, the both cell types are linked with autoimmunity and have
a reciprocal relationship in cellular differentiation under inflammatory milieu. The hypothesis will be
addressed with: 1) Aim 1. Determine if the TLOs in pSS could serve as sites of antigen presentation for
induction of autoantibodies, tolerance or activation, focusing on Treg and Th17 cells; 2) Aim 2. Determine if
patients with pSS have an altered balance of Th17 and Treg immune responses in the peripheral blood
secondary to a defect(s) in Th17 cells and Treg differentiation and function; and 3) Aim 3. Determine if the
altered balance of Th17 and Treg immune responses in peripheral blood correlates with TLOs in the fresh
minor salivary tissues in patients with pSS. These studies will shed new light on the pathogenesis and
treatment of autoimmune diseases including pSS.
原发性干燥综合征(pSS)是一种全身性慢性炎症性自身免疫性疾病
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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Insoo Kang其他文献
Insoo Kang的其他文献
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