Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory disease
回肠炎症性疾病中簇细胞功能、谱系和结构的异质性
基本信息
- 批准号:10396926
- 负责人:
- 金额:$ 4.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-01 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:AblationArchitectureBiological AssayCellsCellular biologyComplexCrohn&aposs diseaseDiseaseEpithelialHeterogeneityImmune responseImmunofluorescence ImmunologicInflammationInflammatoryInflammatory Bowel DiseasesInjuryIntestinal DiseasesIntestinesMicrobeMucous MembraneProstaglandin ProductionProstaglandinsResearchRoleStructureTherapeuticUlcerative Colitisexperimental studyimmunoregulationinflammatory disease of the intestineinnovationknockout genemicrobiomemouse modelnovelrestorationsingle cell sequencing
项目摘要
PROJECT SUMMARY/ABSTRACT
Inflammatory bowel disease (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), is a
complex group of intestinal disorders that results in injury to the epithelium exposing the host to
the luminal microbes. Tuft cells have recently been identified as a responder to the microbiome,
where they can secrete damage-restitution molecules such as prostaglandins. Furthermore, our
lab has successfully demonstrated that tuft cells promote the restoration of intestinal architecture
in ileal inflammatory disease. In this supplement, we propose innovative experimental and
computational approaches to decipher the effector molecules downstream of tuft cells that
modulate inflammation. We will use mouse models where of tuft cell ablation and tuft cell specific
gene knockout to determine whether prostaglandin production from tuft cells is responsible for
their immunomodulatory effects. The epithelial and microenvironmental mechanisms responsible
for these changes will be assayed by single-cell sequencing and multiplex immunofluorescence.
Through our findings, we aim to make significant contributions to the current understanding of tuft
cell biology and inflammation in the intestine. Ultimately, this research will allow us to better
understand where tuft cells act in IBD and expand the pool of targets in this complex, multifactorial
disease.
项目总结/摘要
炎症性肠病(IBD),如克罗恩病(CD)和溃疡性结肠炎(UC),是一种与肠道疾病相关的疾病。
一组复杂的肠道疾病,导致上皮损伤,使宿主暴露于
腔微生物。簇细胞最近被鉴定为对微生物组的应答者,
在那里它们可以分泌修复损伤的分子,比如野牡丹素。而且我们的
实验室已经成功地证明,毛簇细胞促进肠道结构的恢复,
回肠炎性疾病。在本补充中,我们提出了创新的实验和
计算方法来破译簇细胞下游的效应分子,
调节炎症。我们将使用小鼠模型,其中簇细胞消融和簇细胞特异性
基因敲除以确定毛簇细胞产生的前列腺素是否负责
其免疫调节作用。上皮和微环境机制负责
这些变化将通过单细胞测序和多重免疫荧光进行分析。
通过我们的发现,我们的目标是为目前对簇绒的理解做出重大贡献。
细胞生物学和肠道炎症。最终,这项研究将使我们能够更好地
了解丛状细胞在IBD中的作用,并在这个复杂的,多因素的
疾病
项目成果
期刊论文数量(0)
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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Ken S Lau其他文献
Ken S Lau的其他文献
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{{ truncateString('Ken S Lau', 18)}}的其他基金
Co-Evolution Mechanisms of Pre-Cancer-Immune Interactions in Shaping Adaptive Cytotoxicity and Myeloid-Derived Suppression
形成适应性细胞毒性和骨髓源性抑制的癌前免疫相互作用的共同进化机制
- 批准号:
10518849 - 财政年份:2022
- 资助金额:
$ 4.72万 - 项目类别:
Shaping of the Microenvironment in Colonic Pre-Cancer by Epithelia and Microbiota
上皮细胞和微生物群对结肠癌前期微环境的塑造
- 批准号:
10697365 - 财政年份:2022
- 资助金额:
$ 4.72万 - 项目类别:
Shaping of the Microenvironment in Colonic Pre-Cancer by Epithelia and Microbiota
上皮细胞和微生物群对结肠癌前期微环境的塑造
- 批准号:
10518845 - 财政年份:2022
- 资助金额:
$ 4.72万 - 项目类别:
Co-Evolution Mechanisms of Pre-Cancer-Immune Interactions in Shaping Adaptive Cytotoxicity and Myeloid-Derived Suppression
形成适应性细胞毒性和骨髓源性抑制的癌前免疫相互作用的共同进化机制
- 批准号:
10697376 - 财政年份:2022
- 资助金额:
$ 4.72万 - 项目类别:
Spatio-temporal dissection of epithelial cell hierarchies in gut inflammation
肠道炎症中上皮细胞层次结构的时空解剖
- 批准号:
9479946 - 财政年份:2017
- 资助金额:
$ 4.72万 - 项目类别:
Spatio-temporal dissection of epithelial cell hierarchies in gut inflammation
肠道炎症中上皮细胞层次结构的时空解剖
- 批准号:
9028442 - 财政年份:2016
- 资助金额:
$ 4.72万 - 项目类别:
Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory disease
回肠炎症性疾病中簇细胞功能、谱系和结构的异质性
- 批准号:
10463073 - 财政年份:2016
- 资助金额:
$ 4.72万 - 项目类别:
Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory disease
回肠炎症性疾病中簇细胞功能、谱系和结构的异质性
- 批准号:
10338048 - 财政年份:2016
- 资助金额:
$ 4.72万 - 项目类别:
Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory disease
回肠炎症性疾病中簇细胞功能、谱系和结构的异质性
- 批准号:
10589928 - 财政年份:2016
- 资助金额:
$ 4.72万 - 项目类别:
Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory disease
回肠炎症性疾病中簇细胞功能、谱系和结构的异质性
- 批准号:
10048223 - 财政年份:2016
- 资助金额:
$ 4.72万 - 项目类别:
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