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: 10396926
• 负责人: Ken S Lau
• 金额: $ 4.72万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10396926
• 关键词: Ablation; Architecture; Biological Assay; Cells; Cellular biology; Complex; Crohn' s disease; Disease; Epithelial; Heterogeneity; Immune response; Immunofluorescence Immunologic; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Injury; Intestinal Diseases; Intestines; Microbe; Mucous Membrane; Prostaglandin Production; Prostaglandins; Research; Role; Structure; Therapeutic; Ulcerative Colitis; experimental study; immunoregulation; inflammatory disease of the intestine; innovation; knockout gene; microbiome; mouse model; novel; restoration; single cell sequencing

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