The role of Foxo1 for intestinal epithelial cells during mucosal immune response

Foxo1在粘膜免疫反应中对肠上皮细胞的作用

• 批准号: 10702653
• 负责人: Chuan Wu
• 金额: $ 41.8万
• 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/10702653
• 关键词: Cell Communication; Cell physiology; Cells; Cytoplasm; Data; Dendritic Cells; Environment; Epithelial Cells; Equilibrium; Exhibits; FOXO1A gene; FOXP3 gene; Goblet Cells; Human Genetics; Immune; Immune Tolerance; Immune response; Immunology; Impairment; Inflammatory Bowel Diseases; Intestines; Mediating; Molecular; Mucins; Mucosal Immune Responses; Mucous body substance; Mus; Pathway interactions; Play; Predisposition; Proteins; Regulatory T-Lymphocyte; Research; Role; T cell response; T-Lymphocyte; Testing; base; effector T cell; genetic linkage; genome wide association study; gut inflammation; gut microbes; high risk; intestinal epithelium; transcription factor

It is known that intestinal epithelial cells (IECs) interact with immune cells to modulate intestinal or systemic immune responses. Dendritic cells (DCs) are one crucial component in maintaining intestinal immune tolerance. However, how IECs and DCs collaborate to maintain the gut immune balance is still unclear. We further found that one transcription factor Foxo1, plays a critical role for IECs function. The loss of Foxo1 within IECs leads to altered mucus layer formation and DCs function. Consequently, mice without Foxo1 in IECs exhibit enhanced susceptibility to intestinal inflammation. We have hypothesized that IEC-derived Foxo1 regulates the IEC-DC interaction for intestinal tolerance via mucin protein. We are currently studying the cellular and molecular mechanisms of how Foxo1 regulates IECs interaction with DCs.

众所周知，肠上皮细胞（IEC）与免疫细胞相互作用，调节肠道或全身免疫反应。树突状细胞（DC）是维持肠道免疫耐受的重要组成部分之一。然而，IEC 和 DC 如何协作维持肠道免疫平衡仍不清楚。我们进一步发现一种转录因子 Foxo1 对 IEC 功能起着至关重要的作用。 IEC 内 Foxo1 的缺失会导致粘液层形成和 DC 功能发生改变。因此，IEC 中没有 Foxo1 的小鼠表现出对肠道炎症的易感性增强。我们假设 IEC 衍生的 Foxo1 通过粘蛋白调节 IEC-DC 相互作用以实现肠道耐受。 我们目前正在研究 Foxo1 如何调节 IEC 与 DC 相互作用的细胞和分子机制。