亲炎性T细胞FOXP3+:克罗恩病的潜在治疗点
Robyn Laura Kosinsky1, Michelle M Gonzalez2, Dominik Saul3
1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Robert Bosch Center for Tumor Diseases, Stuttgart, Germany.
Gastroenterology
|January 11, 2024
概括
研究人员在克罗恩病 (CD) 患者中发现了一种新的益炎性CD4+T细胞类型. 一种药物,沃里诺斯塔特被证明可以恢复这些细胞的正常功能,为CD提供了潜在的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 基因组学就是基因组学.
背景情况:
- 克罗恩氏病 (CD) 发病率在全球范围内正在上升.
- CD4+ T细胞在CD病变发生中的特定作用需要进一步研究.
- 了解CD4+T细胞的转录特征对于阐明CD的慢性炎症至关重要.
研究的目的:
- 进行CD4+T细胞的详细转录分析,这些细胞参与了CD的慢性炎症.
- 为了识别 CD4+ T 细胞分群,这些分群有助于 CD 疾病的发病.
- 探索CD的潜在治疗点.
主要方法:
- 单细胞RNA测序CD4+ T细胞从CD患者和健康对照的阴茎活检.
- 对被测序细胞的聚类分析和基因信号网络分析.
- 实验室功能研究,包括抑制试验和有机培养系统,以验证发现和测试治疗方法.
主要成果:
- 确定了五种不同的FOXP3+调节性T细胞 (Treg) 亚群.
- 证明健康个体的Tregs可以发展成与炎症相关的亚型.
- 预炎症Tregs显示抑制活性受损,细胞因子反应发生变化,在沃里诺斯塔特治疗后观察到正常化.
结论:
- 在CD患者中发现了一种新型的促炎FOXP3+T细胞亚群.
- 开发了一种策略,利用FDA批准的药物vorinostat来向这些细胞.
- 伏利诺斯塔特有效地使基因表达正常化,并在体外恢复了Treg抑制功能.
相关概念视频
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
139
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...
139
T Cell Types and Functions
1.0K
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...
1.0K
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
166
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
166
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
120
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
120
Inflammatory Bowel Disease II: Crohn's Disease
248
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
248
Inflammatory Response
2.0K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
2.0K


