在DSS诱导的大肠炎期间,Wnt5控制骨髓形成和中性粒细胞功能矛盾
Yi Luan1, Jiajia Hu1, Qijun Wang1
1Department of Pharmacology, Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT 06519, USA.
Cell reports
|March 10, 2024
概括
缺乏无翼型MMTV整合部位的家族成员5 (WNT5) 通过增强脏中性粒细胞的产生来保护大肠炎. 这些中性粒细胞抑制T细胞激活,减少自身免疫性疾病的炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 自免疫性疾病 自免疫性疾病
背景情况:
- 中性粒细胞是具有多种功能的关键先天性免疫细胞.
- 外骨髓中性粒细胞在自身免疫性疾病中的作用尚不清楚.
- 骨髓是中性粒细胞生成的主要部位.
研究的目的:
- 调查WNT5在结肠炎期间中性粒细胞可塑性和外骨膜产生的作用.
- 确定WNT5如何影响自身免疫性疾病中的免疫反应.
- 阐明调节炎症中中性粒细胞异质性的机制.
主要方法:
- 使用大肠炎的小鼠模型.
- 分析了 WNT5 表达在脏层细胞中的表达.
- 评估了外骨髓髓形成和中性粒细胞功能.
- 测量CD8+ T细胞激活和抑制能力.
主要成果:
- 缺少WNT5可以保护大肠炎.
- 缺乏WNT5增强了中的外骨髓髓形成.
- 缺少WNT5的小鼠表现出脊髓中性粒细胞增加,并增强了CD8+ T细胞抑制能力.
- 增加中性粒细胞的CD101表达与减少的促炎活性相关.
结论:
- 在大肠炎中,WNT5调节中性粒细胞的可塑性和异质性.
- 脏中性粒细胞的产生在调节炎症结果方面发挥着至关重要的作用.
- 向WNT5可能为肠炎等自身免疫性疾病提供治疗策略.
相关概念视频
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
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...
2.1K
Renewal of Intestinal Stem Cells
2.6K
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...
2.6K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
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.
2.2K
Canonical Wnt Signaling Pathway
8.7K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.7K
Non-Canonical Wnt Signaling Pathways
7.3K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.3K


