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(Primary Sjogren's syndrome,pSS)是一种全身性慢性炎症性自身免疫性疾病,
眼睛干涩,口干。pSS的基本组织病理学特征包括T和B细胞的局灶性浸润
导致组织损伤和慢性炎症。在一些情况下的
组织病理学变化通过称为淋巴样的过程发展成三级淋巴组织或器官(TL)。
新生TLO在细胞组成和组织方面类似于脾和淋巴结。TLOS
可以作为具有淋巴归巢能力的T细胞(幼稚和中枢记忆)募集的场所
细胞)以及它们的活化、增殖和分化发生。CD 4 + T细胞协调免疫
免疫应答可分为辅助性T细胞(Th)1、Th 2和Th 17细胞以及具有调节性T细胞的CD 4 + T细胞。
功能包括叉头框P3(FOXP 3)阳性调节性T细胞(Treg)。虽然T细胞及其
虽然在pSS的唾液组织中发现了细胞因子,但尚不清楚哪种类型的T细胞在pSS的发病中起主导作用。
发病机制该项目调查了pSS患者的平衡改变的假设,
Th 17和Treg免疫应答由慢性炎症引起,伴有淋巴新生,
Th 17细胞和Treg的分化和功能缺陷,基于Th 17细胞有效地
诱导炎症,而Treg抑制它。另外,这两种细胞类型都与自身免疫有关,
炎症环境下细胞分化的相互关系。假设是
目标:1)目标1。确定pSS中的TLO是否可以作为抗原呈递位点,
自身抗体、耐受或活化的诱导,集中于Treg和Th 17细胞; 2)Aim 2.确定是否
pSS患者外周血中Th 17和Treg免疫应答的平衡改变
继发于Th 17细胞和Treg分化和功能的缺陷;和3)Aim 3.确定是否
外周血中Th 17和Treg免疫应答的平衡改变与新鲜组织中的TLO相关。
pSS患者的小唾液组织。这些研究将揭示新的发病机制,
治疗自身免疫性疾病,包括pSS。
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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