Laboratory of Islet Biology and Inflammation, Pennington Biomedical Research Center, Baton Rouge, LA 70808, United States of America; Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, United States of America.
Laboratory of Immunogenetics, Pennington Biomedical Research Center, Baton Rouge, LA 70808, United States of America.
Autoimmun Rev. 2023 Oct;22(10):103414. doi: 10.1016/j.autrev.2023.103414. Epub 2023 Aug 22.
Type 1 diabetes (T1D) develops due to autoimmune targeting of the pancreatic islet β-cells. Clinical symptoms arise from reduced insulin in circulation. The molecular events and interactions between discrete immune cell populations, infiltration of such leukocytes into pancreatic and islet tissue, and selective targeting of the islet β-cells during autoimmunity and graft rejection are not entirely understood. One protein central to antigen presentation, priming of immune cells, trafficking of leukocytes, and vital for leukocyte effector function is the intercellular adhesion molecule-1 (ICAM-1). The gene encoding ICAM-1 is transcriptionally regulated and rapidly responsive (i.e., within hours) to pro-inflammatory cytokines. ICAM-1 is a transmembrane protein that can be glycosylated; its presence on the cell surface provides co-stimulatory functions for immune cell activation and stabilization of cell-cell contacts. ICAM-1 interacts with the β2-integrins, CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1), which are present on discrete immune cell populations. A whole-body ICAM-1 deletion protects NOD mice from diabetes onset, strongly implicating this protein in autoimmune responses. Since several different cell types express ICAM-1, its biology is fundamentally essential for various physiological and pathological outcomes. Herein, we review the role of ICAM-1 during both autoimmunity and islet graft rejection to understand the mechanism(s) leading to islet β-cell death and dysfunction that results in insufficient circulating quantities of insulin to control glucose homeostasis.
1 型糖尿病 (T1D) 是由于自身免疫靶向胰腺胰岛 β 细胞而发展的。临床症状源于循环中胰岛素的减少。分子事件和离散免疫细胞群体之间的相互作用、这些白细胞浸润到胰腺和胰岛组织中，以及自身免疫和移植物排斥过程中胰岛 β 细胞的选择性靶向，这些都不完全清楚。一种在抗原呈递、免疫细胞启动、白细胞运输中起核心作用，对白细胞效应功能至关重要的细胞间黏附分子-1 (ICAM-1)。编码 ICAM-1 的基因转录调控，对促炎细胞因子的反应迅速（即数小时内）。ICAM-1 是一种跨膜蛋白，可以糖基化；其在细胞表面的存在为免疫细胞的激活提供共刺激功能，并稳定细胞-细胞接触。ICAM-1 与β2-整合素、CD11a/CD18（LFA-1）和 CD11b/CD18（Mac-1）相互作用，这些整合素存在于离散的免疫细胞群体中。全身性 ICAM-1 缺失可保护 NOD 小鼠免受糖尿病发作，强烈提示该蛋白在自身免疫反应中起作用。由于几种不同的细胞类型表达 ICAM-1，因此其生物学功能对于各种生理和病理结果是基本必需的。在此，我们回顾了 ICAM-1 在自身免疫和胰岛移植物排斥中的作用，以了解导致胰岛 β 细胞死亡和功能障碍的机制，导致循环中胰岛素不足，无法控制葡萄糖稳态。
