Alteration of function and specificity of TFH in SLE
SLE 中 TFH 功能和特异性的改变
基本信息
- 批准号:10650347
- 负责人:
- 金额:$ 55.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-07-05 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAgreementAnti-DNA AntibodiesAntigen PresentationAntigen Presentation PathwayAutoantibodiesAutoimmuneAutoimmune DiseasesAutoimmunityB-Cell ActivationB-LymphocytesCD4 Positive T LymphocytesCell Differentiation processCell SeparationCell physiologyCellsChronicClinical TrialsCoculture TechniquesComplexDataDendritic CellsDevelopmentDiseaseDisease ProgressionDisease modelEstradiolEstrogen ReceptorsEstrogensFailureFemaleFrequenciesGenderGene ExpressionGene Expression ProfileGenesGenetic Predisposition to DiseaseGlomerulonephritisGonadal Steroid HormonesHelper-Inducer T-LymphocyteHeterogeneityHormonalITGAX geneImmuneImmune System DiseasesIn VitroIndividualKnowledgeLoxP-flanked alleleModelingMusMutationPRDM1 genePathogenesisPathogenicityPathologyPatientsPatternPeripheralPersonsPhenocopyPlayReceptor SignalingRegulationReporterRisk FactorsRoleSelective Estrogen Receptor ModulatorsSex ChromosomesSignal TransductionSpecificitySpleenStructure of germinal center of lymph nodeSystemic Lupus ErythematosusT cell regulationT-LymphocyteT-cell receptor repertoireTestingTherapeuticThymus Glandantigen processingautoreactive B cellautoreactive T cellautoreactivityconditional knockoutdisease phenotypeeffector T cellgenetic risk factorgenome wide association studyhormone regulationin vivoinsightlupus prone micelupus-likemouse modelnanoparticlenovel therapeuticspatient subsetsprecision medicinereceptor-mediated signalingresponserisk variantsystemic autoimmune diseasethymocyteyoung woman
项目摘要
Project Summary/ Abstract
Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease and
pathogenic mechanisms are not well understood. Based on data from SLE patients and GWAS,
we developed a mouse model to phenocopy the expression pattern of the PRDM1 risk allele.
Mice with a selective deficiency of BLIMP1 in dendritic cells (DCs) (Prdm1 CKO mice) develop
SLE with an increased number of T follicular helper cells (TFH) and autoantibodies arising in a
germinal center response. Only female mice develop disease. The central hypothesis for the
proposed studies is that BLIMP1-deficient DCs alter the selection of T cells in the thymus. We
further hypothesize that estrogen and estrogen-receptor mediated signaling play a critical role in
BLIMP1-deficient DC function, altering antigen presentation and synergizing with BLIMP1
deficiency to skew to TFH differentiation. The following aims will address these hypotheses. Aim
1 will determine if the altered TFH repertoire in female Prdm1 CKO mice is determined during
thymic selection. We will identify whether BLIMP1-deficient DCs alter the strength of TCR
signaling to alter the T cell repertoire. We will explore the function of TFH in female Prdm1 CKO
mice and female control mice, and their activation of autoreactive B cells. Aim 2 will
investigate functional changes in DCs and TFH conferred by estrogen receptor signaling. These
studies should suggest therapeutic strategies in a defined subset of SLE patients, and
advance precision medicine in a disease where many agree that the failure of clinical
trials reflects an inadequate understanding of patient heterogeneity.
项目摘要/摘要
项目成果
期刊论文数量(1)
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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Betty Diamond其他文献
Betty Diamond的其他文献
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{{ truncateString('Betty Diamond', 18)}}的其他基金
Origin and function of atypical lymphocyte populations in inflamed tissue in SLE and RA
SLE 和 RA 炎症组织中非典型淋巴细胞群的起源和功能
- 批准号:
10088788 - 财政年份:2021
- 资助金额:
$ 55.16万 - 项目类别:
Origin and function of atypical lymphocyte populations in inflamed tissue in SLE and RA
SLE 和 RA 炎症组织中非典型淋巴细胞群的起源和功能
- 批准号:
10427145 - 财政年份:2021
- 资助金额:
$ 55.16万 - 项目类别:
Origin and function of atypical lymphocyte populations in inflamed tissue in SLE and RA
SLE 和 RA 炎症组织中非典型淋巴细胞群的起源和功能
- 批准号:
10598097 - 财政年份:2021
- 资助金额:
$ 55.16万 - 项目类别:
Effect of Covid-19 engagement of ACE2 on brain health and pathology
Covid-19 与 ACE2 的结合对大脑健康和病理学的影响
- 批准号:
10151985 - 财政年份:2020
- 资助金额:
$ 55.16万 - 项目类别:
Alteration of function and specificity of TFH in SLE
SLE 中 TFH 功能和特异性的改变
- 批准号:
9973185 - 财政年份:2019
- 资助金额:
$ 55.16万 - 项目类别:
Alteration of function and specificity of TFH in SLE
SLE 中 TFH 功能和特异性的改变
- 批准号:
10437692 - 财政年份:2019
- 资助金额:
$ 55.16万 - 项目类别:
Alteration of function and specificity of TFH in SLE
SLE 中 TFH 功能和特异性的改变
- 批准号:
10196943 - 财政年份:2019
- 资助金额:
$ 55.16万 - 项目类别:
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