肠神经系统衍生VIP抑制LGR5+干细胞向分泌系的分化,阻碍2型免疫程序
Manuel O Jakob1,2, Nele Sterczyk3, Sotiria Boulekou3
1Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. manuel.jakob@charite.de.
Nature immunology
|November 25, 2025
概括
肠道神经系统调节肠道上皮干细胞. 这种神经上皮质电路控制细胞生长和分化,影响免疫反应和屏障平衡.
科学领域:
- 神经胃肠病学 神经胃肠病学
- 免疫学 免疫学 免疫学
- 皮质生物学 皮质生物学
背景情况:
- 肠道屏障稳定包括免疫细胞,上皮细胞和微生物群.
- 肠神经系统 (ENS) 协调肠道免疫力,但其在上皮分化中的作用尚不清楚.
研究的目的:
- 研究ENS在调节肠上皮干细胞命运和分化中的作用.
- 为了确定特定的神经上皮电路,参与维持肠道平衡.
主要方法:
- 确定一个神经上皮电路,涉及血管活性肠 (VIP) 阳性神经元和VIPR1+上皮干细胞.
- 对破坏这种电路对上皮细胞群和免疫反应的影响进行分析.
主要成果:
- 阳性VIP肠道神经元抑制VIPR1+上皮干细胞的增殖和分泌分化.
- 干扰导致状细胞扩张,增加插白素-25 (IL-25) 生产,以及2组先天性淋巴细胞 (ILC2) 激活.
- 观察到的2型免疫反应是微生物群独立的,但由IL-25R-ILC2-IL-13轴和饮食调节.
结论:
- 肠道神经系统是上皮细胞命运决定和肠道免疫平衡的关键调节者.
- 这种神经上皮电路补充了保护屏障完整性和粘膜平衡的已知机制.
相关概念视频
Renewal of Intestinal Stem Cells
3.1K
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
3.1K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.4K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.6K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.6K
Physiology of Enteric Nervous System and Gut Health
840
The gastrointestinal tract, responsible for the digestion and absorption of nutrients, is safeguarded by the intestinal barrier, which consists of secretory, physical, and immune components. At the forefront is the secretory barrier, composed of essential elements such as mucus, gut microbiota, and defense proteins. They collaborate to break down food particles, facilitate nutrient absorption, and maintain optimal gut health. These secretory components ensure the smooth functioning of the...
840
Enteric Nervous System: Regulation of GI Motor Activity
1.6K
The Enteric Nervous System (ENS) plays a pivotal role in regulating gastrointestinal or GI motor activity. This complex network of nerves, deeply embedded within the gut wall, responds to changes in the gut environment and receives input from both the autonomic nervous system and the central nervous system. By doing so, the ENS operates various programs tailored to the body's nutritional status and needs.
During periods of fasting, the ENS initiates the migrating myoelectric complex, a...
During periods of fasting, the ENS initiates the migrating myoelectric complex, a...
1.6K
Adult Stem Cells
33.4K
Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
33.4K


