Jiménez-Fernández María, de la Fuente Hortensia, Martín Pilar, Cibrián Danay, Sánchez-Madrid Francisco
Hospital Universitario de la Princesa, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa (IIS-IP), 28006 Madrid, Spain.
Centro Nacional de Investigaciones Cardiovasculares (CNIC), 29029 Madrid, Spain.
EXCLI J. 2023 Mar 16;22:334-351. doi: 10.17179/excli2022-5751. eCollection 2023.
CD69 is an early leukocyte activation marker involved in the regulation of the immune response. Initial studies evaluated its function using monoclonal antibodies until knock-out mice were developed. Subsequently, four ligands for CD69 have been identified, namely galectin-1, S100A8/S100A9 complex, myosin light chains 9 and 12, and oxidized low-density lipoproteins. In addition, several molecules are laterally associated with and regulated by CD69, including calreticulin and two transmembrane receptors, sphingosine-1-phosphate receptor (S1P1) and the heterodimeric amino acid transporter complex SLC7A5-SLC3A2 (LAT1-CD98). Recently, CD69 engagement has been shown to induce the expression of the immunoregulatory receptor programmed cell death-1 (PD-1) in T cells. The molecular signaling induced by CD69 has been explored in different scenarios and cell types. This review provides a perspective on the molecular pathways, ligands and cellular functions known to be regulated by CD69.
CD69是一种参与免疫反应调节的早期白细胞活化标志物。最初的研究使用单克隆抗体评估其功能,直到敲除小鼠被培育出来。随后,已鉴定出CD69的四种配体,即半乳糖凝集素-1、S100A8/S100A9复合物、肌球蛋白轻链9和12以及氧化型低密度脂蛋白。此外,有几种分子与CD69横向相关并受其调节,包括钙网蛋白以及两种跨膜受体,即1-磷酸鞘氨醇受体(S1P1)和异二聚体氨基酸转运复合物SLC7A5-SLC3A2(LAT1-CD98)。最近,已证明CD69的结合可诱导T细胞中免疫调节受体程序性细胞死亡蛋白1(PD-1)的表达。已在不同的情况和细胞类型中探索了由CD69诱导的分子信号传导。本综述提供了关于已知受CD69调节的分子途径、配体和细胞功能的观点。