在TNF媒介性脑膜炎中,B细胞衍生的LTα3和LTα1β2的不同作用
Emma C Erlich1,2, Quazim A Alayo3,4, Ayoung Kim1
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Nature immunology
|September 8, 2025
概括
由B细胞衍生的淋巴毒素-α (LTα) 在克罗恩病病理学中发挥着至关重要的作用,通过增加肠道透性并导致体重减轻. 相反,可溶性LTα3出乎意料地保护这些缓解毒性作用,平衡瘤缩因子 (TNF).
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 炎症性肠道疾病研究研究
背景情况:
- 克罗恩氏病涉及瘤亡因子 (TNF) 和TNF受体.
- B细胞产生TNF受体的配体,包括淋巴毒素α (LTα).
- LTα形成膜结合的LTαβ2,促进三级淋巴组织,以及溶解的LTα3.
研究的目的:
- 为了研究B细胞衍生的LTαβ2和LTα3在克罗恩氏病的脑膜炎中的作用.
- 确定这些配体对TNFΔARE+/-小鼠疾病病理学的特定贡献.
主要方法:
- 使用TNFΔARE+/-小鼠模型治疗克罗恩病.
- 生成B细胞特异性LTβ淘汰小鼠以评估LTαβ2功能.
- 对LTα3进行中和抗体,以评估其作用.
- 监测肠道透性,IgA+血细胞,细胞因子水平和身体/肌肉质量.
主要成果:
- 对于三级淋巴组织而言,B细胞特异性LTβ删除是必要的,但影响风的影响很小.
- B细胞衍生的LTα的丧失显著增加了肠道透性,并减少了IgA+血细胞.
- B细胞衍生的LTα缺乏导致体重减轻,肌肉质量减少和细胞因子升高.
- 中和LTα3加剧了TNF驱动的缓解症类症状.
结论:
- 从B细胞衍生的LTαβ2和LTα3在实验性脑膜炎中具有不同的独立作用.
- LTα3,而不是LTαβ2,对于保持肠道屏障完整性和预防缓冲症至关重要.
- 溶性LTα3通过平衡肠道中TNF诱导的病理表现出保护作用.
相关概念视频
01:24T Cell Types and Functions
2.2K
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...
2.2K
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
506
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...
506
01:29Inflammatory Bowel Disease IV: Pharmacological Management
531
Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
Pharmacologic...
Pharmacologic...
531
01:24B Cell Activation and Differentiation
16.1K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
16.1K
02:26NF-κB-dependent Signaling Pathway
9.8K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
9.8K