在1型糖尿病病原发生过程中的表皮层次结构
Thomas Delong1, Maki Nakayama2,3,4
1Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA Thomas.delong@cuanschutz.edu maki.nakayama@cuanschutz.edu.
Cold Spring Harbor perspectives in medicine
|November 5, 2024
概括
1型糖尿病 (T1D) 涉及T细胞攻击胰岛素产生细胞. 研究人员确定了关键的T细胞表位,包括前胰岛素和混合胰岛素 (HIP),对于理解T1D和开发新疗法至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 自免疫性疾病 自免疫性疾病
背景情况:
- 1型糖尿病 (T1D) 是一种自身免疫性疾病,T细胞破坏胰腺β细胞.
- 了解这些自身反应性T细胞的特定标对于疾病发病研究和治疗开发至关重要.
研究的目的:
- 审查和识别涉及1型糖尿病的关键T细胞表位.
- 要突出前前胰岛素和混合胰岛素 (HIPs) 作为T1D中显著的自身抗原的作用.
- 讨论新的新型表位和区分致病表位与模拟表位的挑战.
主要方法:
- 关于1型糖尿病T细胞表位的文献综述.
- 分析涉及胰岛素B链和C表位的证据.
- 检查新的表位类,包括HIPs,翻译后修饰,拼接变体和缺陷的核糖体产物.
主要成果:
- 胰岛素B链和C表位是T1D岛屿中致病性CD4+和CD8+T细胞的主要标.
- 混合胰岛素 (HIPs) 是一种新发现的人类和小鼠群岛中发现的T1D表位类.
- 各种来源有助于新位,包括修饰和核糖体产物,使位鉴定复杂化.
结论:
- 在T1D中识别特定的,致病性T细胞表位是了解疾病机制的关键.
- 从非致病性模拟物区分疾病驱动性表位仍然是一个重大挑战.
- 发现必要的表位体可能为1型糖尿病的抗原特异性免疫疗法铺平道路.
相关概念视频
Pathophysiology of Diabetes
872
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
872
Diabetes Mellitus: Overview and Type I Subtype
2.5K
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
2.5K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.1K
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...
1.1K
Insulin: Biosynthesis, Chemistry, and Preparation
359
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
359
Antigen Processing Pathways
940
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
MHC Class I: Presenting Endogenous...
940
Insulin Secretory Vesicles
4.8K
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...
4.8K


