Project 2: STAT3 as a trigger for T1D
Project 2: STAT3 as a trigger for T1D
批准号:
10576386
负责人:
Mark S Anderson
金额:
$17.54万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-02-17 至 2027-01-31
关键词:
AccelerationAdoptive TransferAllelesAnimal ModelAnimalsAntigensAutoantibodiesAutoimmuneAutoimmune DiabetesAutoimmunityB-LymphocytesCD8-Positive T-LymphocytesCell SurvivalCell surfaceCellsClinicalCollaborationsCritical PathwaysDefectDevelopmentDiabetes MellitusDiseaseEngineeringEpitheliumFOXP3 geneFamily memberGene ActivationGene ExpressionGenesGeneticGenetic TranscriptionHormonesHumanHuman GeneticsImmuneImmune ToleranceImmune systemInbred NOD MiceInfiltrationInsulinInsulin-Dependent Diabetes MellitusInterleukin-6Knock-in MouseKnowledgeLinkMHC Class II GenesMapsMediatingMendelian disorderMissense MutationModelingMusMutationNatural ImmunityOrganPathway interactionsPatientsPhenotypePhosphorylationPlayPopulationPredispositionProliferatingRegulatory T-LymphocyteReportingResearch PersonnelRoleSignal TransductionStat3 proteinStudy modelsSyndromeT-LymphocyteThymic epithelial cellThymus GlandTimeTissuesTranscription Factor 3ValidationVariantWorkadaptive immunitycentral tolerancecytokinecytopeniaexome sequencinggain of functiongain of function mutationimprovedinsightinsulin dependent diabetes mellitus onsetinsulitisisletlymphadenopathymouse modelnovelperipheral bloodperipheral tolerancesuccesssynergismtranscription factortransmission process
中文摘要
项目总结/摘要
与1型糖尿病发展密切相关的单基因疾病已经被发现,
为解开控制这种疾病的关键途径提供了信息。成功使用此
方法包括AIRE和FOXP 3的研究,这些研究为确定
胸腺和T调节细胞,保持1型糖尿病的检查。在这里,我们将利用最近的知识,
STAT 3中的功能获得突变(GOF)与1型糖尿病的发生密切相关,
通过开发一个强大的综合症动物模型。
我们的具体目标是:
目的1:在新型自身免疫性糖尿病小鼠模型中模拟STAT 3 GOF的作用
(NOD.STAT3K392R/+)
目的2:鉴定和表征NOD.STAT3K392R/+缺陷的关键免疫细胞群体
模型和具有相似STAT 3 GOF突变的患者中
目的3:确定在STAT 3 GOF模型中中枢耐受性是如何潜在改变的
这些研究将与PPG项目1(库珀)和3(Marson)密切合作进行,并将
有助于我们更好地理解免疫耐受是如何由STAT 3控制的,以及STAT 3基因的改变是如何影响免疫耐受的。
这种分子可以刺激1型糖尿病。
英文摘要
Project Summary/Abstract
Monogenic diseases that have a close association with the development of type 1 diabetes have been
informative for unraveling critical pathways that keep this disease in check. Examples of success using this
approach include the study of AIRE and FOXP3 which have been informative for identifying pathways in the
thymus and T regulatory cells that keep type 1 diabetes in check. Here, we will leverage the recent knowledge
that gain of function mutations (GOF) in STAT3 are tightly associated with the development of type 1 diabetes
by developing a robust animal model of the syndrome.
Our specific aims are:
Aim 1: Model the effects of STAT3 GOF in a novel mouse model of autoimmune diabetes
(NOD.STAT3K392R/+)
Aim 2: Identify and characterize key immune cell populations that are defective in the NOD.STAT3K392R/+
model and in patients with similar STAT3 GOF mutations
Aim 3: Identify how central tolerance is potentially altered in STAT3 GOF models
These studies will be performed in close collaboration with PPG projects 1 (Cooper) and 3 (Marson) and will
help improve our understanding of how the immune tolerance is controlled by STAT3 and how alterations in
this molecule can provoke type 1 daibetes.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Administrative Core
-
批准号:10328098
-
项目类别:
-
资助金额:$8.08万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
STAT3 variants as a rheostat of immune tolerance
-
批准号:10328097
-
项目类别:
-
资助金额:$176.58万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
Tuning peptide specifities for T cell tolerance in Type 1 diabetes
-
批准号:10630946
-
项目类别:
-
资助金额:$46.85万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
Alterations of leukocyte integrin signaling leading to diabetes and autoimmunity
-
批准号:10502136
-
项目类别:
-
资助金额:$64.67万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
Project 2: STAT3 as a trigger for T1D
-
批准号:10328102
-
项目类别:
-
资助金额:$40.38万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
Core A: Mouse Core
-
批准号:10328099
-
项目类别:
-
资助金额:$24.11万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
Tuning peptide specifities for T cell tolerance in Type 1 diabetes
-
批准号:10503923
-
项目类别:
-
资助金额:$44.95万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
Alterations of leukocyte integrin signaling leading to diabetes and autoimmunity
-
批准号:10683384
-
项目类别:
-
资助金额:$66.63万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
Core A: Mouse Core
-
批准号:10576378
-
项目类别:
-
资助金额:$24.11万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
STAT3 variants as a rheostat of immune tolerance
-
批准号:10576375
-
项目类别:
-
资助金额:$176.56万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
Administrative Core
-
批准号:10576377
-
项目类别:
-
资助金额:$8.08万
-
财政年份:2022
-
负责人:Mark S Anderson
-
依托单位:
Immune Tolerance Network
-
批准号:10625931
-
项目类别:
-
资助金额:$684.91万
-
财政年份:2021
-
负责人:Mark S Anderson
-
依托单位:
Modeling autoimmune pathogenesis and beta cell destruction by T1D immune systems
-
批准号:10179371
-
项目类别:
-
资助金额:$95.17万
-
财政年份:2019
-
负责人:Mark S Anderson
-
依托单位:
Modeling autoimmune pathogenesis and beta cell destruction by T1D immune systems
-
批准号:10413178
-
项目类别:
-
资助金额:$95.17万
-
财政年份:2019
-
负责人:Mark S Anderson
-
依托单位:
Modeling autoimmune pathogenesis and beta cell destruction by T1D immune systems
-
批准号:10020398
-
项目类别:
-
资助金额:$95.13万
-
财政年份:2019
-
负责人:Mark S Anderson
-
依托单位:
Modeling autoimmune pathogenesis and beta cell destruction by T1D immune systems
-
批准号:10762177
-
项目类别:
-
资助金额:$42.5万
-
财政年份:2019
-
负责人:Mark S Anderson
-
依托单位:
Using human stem cell-derived thymic epithelium to remodel T1D immune tolerance
-
批准号:9106605
-
项目类别:
-
资助金额:$57.84万
-
财政年份:2016
-
负责人:Mark S Anderson
-
依托单位:
Core A - Animal core
-
批准号:9151386
-
项目类别:
-
资助金额:$25.24万
-
财政年份:2016
-
负责人:Mark S Anderson
-
依托单位:
Project 1 - Central thymic tolerance as a major checkpoint in T1D
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批准号:9151388
-
项目类别:
-
资助金额:$39.63万
-
财政年份:2016
-
负责人:Mark S Anderson
-
依托单位:
Disruption of T cell tolerance in type 1 diabetes
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批准号:9291418
-
项目类别:
-
资助金额:$162.91万
-
财政年份:2016
-
负责人:Mark S Anderson
-
依托单位:
海外基金