The Role of Toll-like Receptor 4 Positive T Cells in Intestinal Immune Regulation
The Role of Toll-like Receptor 4 Positive T Cells in Intestinal Immune Regulation
批准号:
8484392
负责人:
Mirac Nedim Ince
金额:
$14.75万
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
项目状态:
已结题
起止时间:
2009-07-15 至 2014-06-30
关键词:
Adverse effectsAdvisory CommitteesAnimalsAntigensAppointmentAwardBacteriaCD14 geneCell Culture TechniquesCellsColitisDevelopmentDisease modelDistalElementsEquilibriumExposure toFacultyFellowshipGastroenterologyGenerationsHelminthsImmuneImmune responseImmunologyIn VitroIndiumIndividualInfectionInflammationInflammatory Bowel DiseasesInflammatory disease of the intestineInstructionIntestinesIowaLamina PropriaLeadLipopolysaccharidesMaintenanceMediatingMedicalMentorshipModelingMolecular and Cellular BiologyMononuclearMouse StrainsMucous MembraneMusNematodaNematospiroides dubiusParasitesPathway interactionsPharmaceutical PreparationsPhysiciansPrincipal InvestigatorProductionProteinsRNAReceptor SignalingRegulationRegulatory T-LymphocyteResearchRoleScientistSignal PathwaySignal TransductionT cell responseT-LymphocyteTestingToll-like receptorsTransforming Growth Factor betaUniversitiescareer developmentcommensal microbescytokineimmunoregulationmembermouse modelmouse toll-like receptor 4novelpathogenpreventprofessorreceptorresearch studyresponseskillstoll-like receptor 4
中文摘要
本应用旨在探讨toll样受体4阳性(TLR4) T细胞在调节细胞凋亡中的作用
英文摘要
This application proposes to investigate the role of toll-like receptor 4 positive (TLR4) T cells in regulating
inflammatory bowel disease in mouse models. TLR4+ T lymphocytes emerge during immune modulatory
helminth infection in the intestine. They recognize bacterial lipopolysaccharide (LPS) and produce immune
regulatory TGF-beta but not proinflammatory cytokines, when stimulated with LPS. We hypothesize that
LPS-stimulated mucosal T cell TGF-beta secretion is important for intestinal immune regulation. We propose
to test our hypothesis in H. polygyrus infection model in uninflamed wild-type or colitic animals and in mice
genetically deficient for proteins that participate in TLR4 signaling pathway, like MyD88-/- or TRIF-/- mouse
strains. In certain experiments we plan to employ pharmacologic agents or complementary short inhibitory
RNA (sIRNA) contructs to inhibit certain elements of TLR4 signaling pathway. Specific Aim #1: We will
determine phenotypic and functional changes in TLR4+ intestinal T cells following LPS stimulation. Specific
Aim #2: We will define the signaling elements in intestinal TLR4+ T cells that lead to TGF-beta production.
Specific Aim #3: We will identify the role of TLR4+ T cells in the induction or maintenance of intestinal
immune balance in mouse models of colitis. This proposal may lead to the identification of novel cellular
proteins important in the control of IBD. Targeting these molecules by pharmacologic agents may lead to
potent and safer medical management of inflammatory bowel disease.
The long-term objective of this proposal is to advance the principal investigator to an independent physician
scientist in gastroenterology and mucosal immunology with significant background in cellular and molecular
biology. The applicant has completed fellowship in gastroenterology at the University of Iowa in 2007 and is
in his first year of appointment as an assistant professor on tenure track. The research will take place at the
University of Iowa under the mentorship of Drs. David Elliott, Paul Rothman and Gary Hunninghake. In
addition, an advisory committee of faculty members will provide career development advice. The award
would allow the principal investigator to master research skills in cellular and molecular biology.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Regulation of graft versus host disease with in vivo generated regulatory T cells
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批准号:9240776
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项目类别:
-
资助金额:$0.0万
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财政年份:2017
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负责人:Mirac Nedim Ince
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依托单位:
Mixed Chimerism-Dependent Tolerance After Myeloablative Bone Marrow Transplantation
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批准号:10449110
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项目类别:
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资助金额:$0.0万
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财政年份:2017
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负责人:Mirac Nedim Ince
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依托单位:
Mixed Chimerism-Dependent Tolerance After Myeloablative Bone Marrow Transplantation
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批准号:10259947
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项目类别:
-
资助金额:$0.0万
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财政年份:2017
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负责人:Mirac Nedim Ince
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依托单位:
The Role of Toll-like Receptor 4 Positive T Cells in Intestinal Immune Regulation
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批准号:8082745
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项目类别:
-
资助金额:$14.75万
-
财政年份:2009
-
负责人:Mirac Nedim Ince
-
依托单位:
The Role of Toll-like Receptor 4 Positive T Cells in Intestinal Immune Regulation
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批准号:8312727
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项目类别:
-
资助金额:$14.75万
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财政年份:2009
-
负责人:Mirac Nedim Ince
-
依托单位:
The Role of Toll-like Receptor 4 Positive T Cells in Intestinal Immune Regulation
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批准号:7740999
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项目类别:
-
资助金额:$14.75万
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财政年份:2009
-
负责人:Mirac Nedim Ince
-
依托单位:
The Role of Toll-like Receptor 4 Positive T Cells in Intestinal Immune Regulation
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批准号:7890362
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项目类别:
-
资助金额:$14.75万
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财政年份:2009
-
负责人:Mirac Nedim Ince
-
依托单位:
海外基金