Understanding NLRP6 function in intestinal homeostasis
了解 NLRP6 在肠道稳态中的功能
基本信息
- 批准号:10393573
- 负责人:
- 金额:$ 40.02万
- 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:2019-07-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectBacteriaCASP1 geneCaspaseCellsChronicCitrobacter rodentiumColitisColonColon CarcinomaComplexDataDevelopmentEpithelialFamily memberGoalsHematopoieticHomeostasisHost DefenseImpairmentInfectionInflammasomeInflammationInflammatoryInflammatory Bowel DiseasesInflammatory ResponseInterferonsInterleukin-10Interleukin-18IntestinesLigandsMaintenanceMediatingMicrobeMucous body substanceMusMyeloid CellsPathogenesisPathologyPathway interactionsPattern recognition receptorPhenotypePlayPredispositionProductionPublishingRegulationReportingResistanceResolutionRoleSignal PathwaySignal TransductionStructureTimeTissuesWild Type Mouseantimicrobialantimicrobial peptidechemically induced colitischemokinechronic inflammatory diseasecolon tumorigenesiscommensal bacteriacytokinedysbiosisenteric virus infectionepithelial injurygerm free conditiongut homeostasisgut inflammationgut microbiomegut microbiotaintestinal epitheliumintestinal homeostasismacrophagemicrobialmicrobial communitymicrobiome alterationmortalitymouse modelneutrophilpathogenpathogenic bacteriaprotective effectreceptorrepairedtissue injurytreatment strategytumor
项目摘要
PROJECT SUMMARY
Nod-like receptors (NLRs) are intracellular pattern-recognition receptors that are involved in host
defense, but have emerged as critical players in the maintenance of tissue homeostasis,
especially within the intestine. Capable of sensing microbial products as well as endogenous
ligands related to tissue injury, NLRs activate multiple downstream inflammatory signaling
pathways, including the inflammasome, to promote the production of cytokines and chemokines
important for pathogen clearance and the timely repair of intestinal epithelial damage. There is
also increasing evidence that NLRs participate in the regulation of the gut microbiome.
Consequently, mice that are deficient in certain NLRs have altered microbiomes associated with
increased susceptibility to colitis and colon tumorigenesis. In particular, mice deficient in NLRP6
develop more severe inflammation and tumors compared to wildtype mice in mouse models of
inflammatory bowel disease and inflammation-associated colon cancer. This phenotype is
associated with impaired IL-18 production and an altered microbiome. However, the cellular
mechanisms by which NLRP6 mediate its protective effects within the colon is unclear. NLRP6
is highly expressed in the epithelium and consistently, there have been multiple reports that
demonstrate epithelial-specific roles for NLRP6, including the production of IL-18, antimicrobial
peptides, and mucus. However, NLRP6 expression can also be induced in hematopoietic cells,
and our published data suggests important roles for NLRP6 in the regulation of IL-18 and intestinal
inflammatory responses in hematopoietic cells. Thus, the mechanism by which NLRP6 protects
against colitis is likely to be complex. The goal of the current proposal is to further delineate
NLRP6 function in myeloid cells and the inflammatory signaling pathways NLRP6 engages in to
affect resistance to intestinal pathology.
项目总结
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)
NOD1 and NOD2 in inflammatory and infectious diseases.
- DOI:10.1111/imr.12902
- 发表时间:2020-09
- 期刊:
- 影响因子:8.7
- 作者:Trindade BC;Chen GY
- 通讯作者:Chen GY
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GRACE Y. CHEN其他文献
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{{ truncateString('GRACE Y. CHEN', 18)}}的其他基金
Targeting cancer stem-like cells and inflammation for colon cancer chemoprevention
针对癌症干细胞样细胞和炎症进行结肠癌化学预防
- 批准号:
10650910 - 财政年份:2023
- 资助金额:
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Dietary fiber and soy protein-based microbiome metabolites for IBD prevention
基于膳食纤维和大豆蛋白的微生物组代谢物用于预防 IBD
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10607658 - 财政年份:2018
- 资助金额:
$ 40.02万 - 项目类别:
(10.) The Gut Microbiome and Responses to Neoadjuvant Chemoradiation in Rectal Cancer Patients
(10.) 直肠癌患者的肠道微生物群和对新辅助放化疗的反应
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$ 40.02万 - 项目类别:
(10.) The Gut Microbiome and Responses to Neoadjuvant Chemoradiation in Rectal Cancer Patients
(10.) 直肠癌患者的肠道微生物群和对新辅助放化疗的反应
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9100263 - 财政年份:2016
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$ 40.02万 - 项目类别:
Identifying bacterial regulators of tumorigenesis
识别肿瘤发生的细菌调节因子
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8982222 - 财政年份:2014
- 资助金额:
$ 40.02万 - 项目类别:
Identifying bacterial regulators of tumorigenesis
识别肿瘤发生的细菌调节因子
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8814012 - 财政年份:2014
- 资助金额:
$ 40.02万 - 项目类别:
Regulation of intestinal inflammation and tumorigenesis by Nlrp6
Nlrp6 对肠道炎症和肿瘤发生的调节
- 批准号:
8606443 - 财政年份:2013
- 资助金额:
$ 40.02万 - 项目类别:
Regulation of intestinal inflammation and tumorigenesis by Nlrp6
Nlrp6 对肠道炎症和肿瘤发生的调节
- 批准号:
8436792 - 财政年份:2013
- 资助金额:
$ 40.02万 - 项目类别:
Role of the immune receptor Nod1 in inflammation-associated colon tumorigenesis
免疫受体Nod1在炎症相关结肠肿瘤发生中的作用
- 批准号:
7912863 - 财政年份:2008
- 资助金额:
$ 40.02万 - 项目类别:
Role of the immune receptor Nod1 in inflammation-associated colon tumorigenesis
免疫受体Nod1在炎症相关结肠肿瘤发生中的作用
- 批准号:
7588189 - 财政年份:2008
- 资助金额:
$ 40.02万 - 项目类别:
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