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

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.
项目摘要 Nod-like receptor(NLR)是一种细胞内的模式识别受体,参与宿主细胞的免疫应答。 防御,但已成为维持组织稳态的关键参与者, 尤其是在肠内。能够感知微生物产物以及内源性 与组织损伤相关的配体、NLR激活多种下游炎症信号传导 途径,包括炎性体,以促进细胞因子和趋化因子的产生 对于病原体清除和肠上皮损伤的及时修复非常重要。有 也有越来越多的证据表明NLR参与肠道微生物组的调节。 因此,缺乏某些NLR的小鼠改变了与NLR相关的微生物组。 增加对结肠炎和结肠肿瘤的易感性。特别地,NLRP 6缺陷的小鼠 在小鼠模型中,与野生型小鼠相比, 炎症性肠病和炎症相关结肠癌。该表型 与IL-18产生受损和微生物组改变有关。然而,Cellular NLRP 6在结肠内介导其保护作用的机制尚不清楚。NLRP 6 在上皮细胞中高度表达,并且一直有多项报道, 证实了NLRP 6的上皮特异性作用,包括产生IL-18、抗微生物 肽和粘液。然而,NLRP 6表达也可以在造血细胞中诱导, 我们发表的数据表明,NLRP 6在调节IL-18和肠道炎症中起重要作用。 造血细胞的炎症反应。因此,NLRP 6的保护机制 对抗结肠炎的方法可能很复杂本提案的目标是进一步界定 NLRP 6在骨髓细胞中发挥作用,并且NLRP 6参与炎症信号传导途径, 影响对肠道病变的抵抗力。

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

GRACE Y. CHEN的其他文献

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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:
    $ 40.02万
  • 项目类别:
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
  • 批准号:
    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
  • 批准号:
    9250105
  • 财政年份:
    2016
  • 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
  • 批准号:
    9100263
  • 财政年份:
    2016
  • 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
  • 批准号:
    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
  • 批准号:
    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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