Inter- and intra-epithelial regulation for intestinal barrier integrity

肠屏障完整性的上皮间和上皮内调节

• 批准号: 10926306
• 负责人: Chuan Wu
• 金额: $ 36.07万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926306
• 关键词: Antigens; Autophagocytosis; Blood Circulation; Cell Line; Cells; Communication; Complex; Diet; Disease; Enterocytes; Epithelial Cells; Epithelium; Exposure to; Gastrointestinal Diseases; Goblet Cells; Homeostasis; Immune; Immune system; Immunologics; Inflammation; Intervention; Intestinal Mucosa; Intestinal permeability; Intestines; Invaded; Mediating; Microbe; Mucous Membrane; Mucous body substance; Nutrient; Pathogenesis; Physiology; Play; Proteins; Regulation; Role; Structure; Symbiosis; Tissues; Toxin; Work; cell type; commensal bacteria; gut inflammation; gut microbiome; host-microbe interactions; intestinal barrier; intestinal epithelium; intraepithelial; microbial; microbial host; microorganism; pathogen; prevent; uptake

The intestinal epithelium forms the first line of defense against bacterial invasion while providing a proper microenvironment to support microbial symbiosis. The diverse functions of intestinal epithelial cells have been demonstrated to play distinct roles in modulating the homeostatic host-microbial interactions for tissue physiology. The integrity of this barrier is crucial for preventing the entry of harmful pathogens and toxins from the gut into the bloodstream. The regulation of intestinal barrier integrity involves both inter- and intra-epithelial mechanisms. Dysregulation of these mechanisms can lead to increased intestinal permeability, inflammation, and a range of gastrointestinal diseases. Moreover, IECs function as one major component to compromise the intestinal barrier, facilitating the establishment of an immunological interface to support commensal bacteria colonization while protecting tissue from pathogen invasion. We demonstrate that autophagy in goblet cells plays a critical role in establishing commensalism and maintaining intestinal barrier integrity. Further, our work suggests that goblet cell-mediated protein sialyation is crucial for intestinal mucus integrity and host-microbial homeostasis5. Thus, understanding inter- and intra-epithelial regulation and the interactions between the gut microbiome and the host can shed light on the pathogenesis of intestinal inflammation and provide new avenues for disease intervention and treatment.

肠上皮形成了抵抗细菌入侵的第一道防线，同时提供了适当的微环境以支持微生物共生。肠上皮细胞的多种功能已被证明在调节组织生理学的稳态宿主-微生物相互作用中发挥独特的作用。这一屏障的完整性对于防止有害病原体和毒素从肠道进入血液至关重要。肠屏障完整性的调节涉及上皮间和上皮内机制。这些机制的失调可导致肠通透性增加、炎症和一系列胃肠道疾病。此外，IEC作为一种主要成分发挥作用，破坏肠道屏障，促进建立免疫界面以支持肠道细菌定植，同时保护组织免受病原体入侵。我们证明了杯状细胞中的自噬在建立肠道屏障和维持肠道屏障完整性方面起着关键作用。此外，我们的工作表明，杯状细胞介导的蛋白质唾液酸化对于肠粘液完整性和宿主-微生物稳态至关重要5。因此，了解上皮内和上皮间的调节以及肠道微生物组与宿主之间的相互作用可以揭示肠道炎症的发病机制，并为疾病干预和治疗提供新的途径。

项目成果

Interleukin-33 Promotes Serotonin Release from Enterochromaffin Cells for Intestinal Homeostasis.

白介素-33促进肠球毒细胞从肠道稳态中释放5-羟色胺。

• DOI: 10.1016/j.immuni.2020.10.014
• 发表时间: 2021-01-12
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Chen Z;Luo J;Li J;Kim G;Stewart A;Urban JF Jr;Huang Y;Chen S;Wu LG;Chesler A;Trinchieri G;Li W;Wu C
• 通讯作者: Wu C

Cathepsin W restrains peripheral regulatory T cells for mucosal immune quiescence.

组织蛋白酶W限制外周调节T细胞以进行粘膜免疫静止。

• DOI: 10.1126/sciadv.adf3924
• 发表时间: 2023-07-14
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: Li, Jian;Chen, Zuojia;Kim, Girak;Luo, Jialie;Hori, Shohei;Wu, Chuan
• 通讯作者: Wu, Chuan

Reciprocal Interactions Between Regulatory T Cells and Intestinal Epithelial Cells.

• DOI: 10.3389/fimmu.2022.951339
• 发表时间: 2022
• 期刊: FRONTIERS IN IMMUNOLOGY
• 影响因子: 7.3
• 作者: Jiang, Zhiqiang;Wu, Chuan
• 通讯作者: Wu, Chuan