艾尔通过高亲和性T细胞克隆的胸膜切割来调节对胰岛素的耐受性
Jennifer A Smith1, Benjamin T K Yuen1, Whitney Purtha1
1Diabetes Center, University of California San Francisco, San Francisco, CA 94143.
概括
由Aire调节的胰岛素的胸膜表达对于去除高亲和性T细胞至关重要. 它的缺失使这些细胞能够逃脱负面选择,影响1型糖尿病 (T1D) 病原发生.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 遗传学 是一个遗传学.
背景情况:
- 胰岛素是1型糖尿病 (T1D) 病原发生的关键自身抗原.
- 胸膜上皮细胞表达胰岛素,由自身免疫调节器 (Aire) 调节,被认为可以诱导对胰岛素的耐受性.
- 对胰岛素特异性T细胞上这种胸膜选择过程的直接证据是有限的.
研究的目的:
- 调查依赖于Aire的胸膜胰岛素表达在胰岛素特异性T细胞选择中的作用.
- 在缺氧小鼠中识别和描述胰岛素特异性T细胞的T细胞受体 (TCR).
主要方法:
- 利用T细胞受体转基因模型来检测胸膜选择.
- 从缺氧小鼠中对胰岛素特异性CD4+T细胞进行了分类和测序.
- 在Air-deficient和野生型宿主中对特定的TCR克隆进行模拟的胸膜选择.
主要成果:
- 在空气缺乏小鼠中鉴定出具有高亲和力对胰岛素/MHC配体的独特TCR克隆.
- 证明了一个高亲和度的TCR克隆可以在没有胸膜Aire的情况下逃避负选择.
- 展示了胸膜Aire在消除潜在的自身反应性T细胞中的关键作用.
结论:
- 胸膜胰岛素表达对于切割和去除高亲和性胰岛素特异性T细胞至关重要.
- 胸腺中空气介导的负选择对于维持对胰岛素的自我耐受性至关重要.
- 这个过程中的缺陷可能会导致T1D的发展.
相关概念视频
01:28Insulin: The Receptor and Signaling Pathways
1.2K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.2K
01:20Special Features of Adaptive Immunity
804
The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
804
01:27Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.2K
The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
Insulin and C-peptide are...
1.2K
01:40Cell-mediated Immune Responses
68.2K
Overview
68.2K
01:16Hormones Regulating Blood Glucose
3.3K
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
3.3K
01:05Insulin Secretory Vesicles
4.9K
Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
4.9K