炎症诱导的IgA+细胞破坏抗肝癌免疫力
Shabnam Shalapour1, Xue-Jia Lin1,2, Ingmar N Bastian1
1Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego (UCSD), 9500 Gilman Drive, La Jolla, California 92093, USA.
Nature
|November 17, 2017
概括
脂肪肝的慢性炎症通过增加免疫球蛋白A (IgA+) 生产细胞促进癌症. 这些细胞抑制细胞毒性CD8+T淋巴细胞,阻碍早期癌症检测并促进瘤生长.
科学领域:
- 免疫学
- 肝病学
- 癌症学
背景情况:
- 适应性免疫在早期癌症发展中的作用仍在争论中.
- 非酒精性脂肪肝 (NAFLD) 与慢性炎症和纤维化有关.
- 肝脏中的免疫球蛋白A (IgA+) 生产细胞在NAFLD中积累.
研究的目的:
- 在NAFLD的背景下研究IgA+细胞在肝细胞癌 (HCC) 的作用.
- 阐明IgA+细胞影响瘤微环境和免疫监测的机制.
主要方法:
- 从人类和老鼠NAFLD模型中分析肝脏组织.
- 鉴定IgA+细胞表型,包括编程死亡配体1 (PD- L1) 和互白素-10 (IL-10) 的表达.
- 评估IgA+细胞对细胞毒性CD8+T淋巴细胞功能和HCC发育的影响.
主要成果:
- 在NAFLD中观察到表达PD- L1和IL-10的IgA+细胞的积累.
- 这些IgA+细胞直接抑制肝细胞毒性CD8+T淋巴细胞.
- CD8+ T细胞的消耗加速了HCC,同时抑制了IgA+细胞的产生减弱了肝癌并促进了HCC的回归.
结论:
- 炎症诱导的IgA+细胞抑制细胞毒性CD8+T淋巴细胞激活是NAFLD相关的瘤促进机制.
- 针对IgA+细胞的产生为肝癌提供了潜在的治疗策略.
相关概念视频
Gastritis-II: Pathophysiology
1.4K
Gastritis is marked by disruption of the mucosal barrier that usually protects the stomach tissue from digestive juices and manifests in acute and chronic forms.
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
1.4K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
602
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
602
Liver Regeneration
4.5K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
4.5K
T Cell Types and Functions
2.7K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
2.7K
Inflammatory Bowel Disease I: Ulcerative Colitis
1.2K
Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
1.2K
Tumor Immunotherapy
2.0K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.0K


