Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hartmannstraße 14, 91052 Erlangen, Germany.
Comprehensive Cancer Center Erlangen European Metropolitan Area of Nuremberg (CCC ER-EMN), Östliche Stadtmauerstraße 30, 91054 Erlangen, Germany.
Int J Mol Sci. 2022 Aug 2;23(15):8599. doi: 10.3390/ijms23158599.
Programmed Cell Death 1 Ligand 1 (PD-L1, CD274, B7-H1) is a transmembrane protein which is strongly involved in immune modulation, serving as checkpoint regulator. Interaction with its receptor, Programmed Cell Death Protein 1 (PD-1), induces an immune-suppressive signal, which modulates the activity of T cells and other effector cells. This mediates peripheral tolerance and contributes to tumor immune escape. PD-L1 became famous due to its deployment in cancer therapy, where blockage of PD-L1 with the help of therapeutic antagonistic antibodies achieved impressive clinical responses by reactivating effector cell functions against tumor cells. Therefore, in the past, the focus has been placed on PD-L1 expression and its function in various malignant cells, whereas its role in healthy tissue and diseases apart from cancer remained largely neglected. In this review, we summarize the function of PD-L1 in non-cancerous cells, outlining its discovery and origin, as well as its involvement in different cellular and immune-related processes. We provide an overview of transcriptional and translational regulation, and expression patterns of PD-L1 in different cells and organs, and illuminate the involvement of PD-L1 in different autoimmune diseases as well as in the context of transplantation and pregnancy.
程序性细胞死亡蛋白 1 配体 1（PD-L1、CD274、B7-H1）是一种跨膜蛋白，它在免疫调节中起着重要作用，作为检查点调节剂。与它的受体程序性细胞死亡蛋白 1（PD-1）相互作用会诱导免疫抑制信号，从而调节 T 细胞和其他效应细胞的活性。这介导外周耐受，并有助于肿瘤免疫逃逸。PD-L1 因其在癌症治疗中的应用而声名鹊起，通过使用治疗性拮抗抗体阻断 PD-L1，可以通过重新激活效应细胞对肿瘤细胞的功能来实现令人印象深刻的临床反应。因此，过去的研究重点主要放在 PD-L1 在各种恶性细胞中的表达及其功能上，而其在健康组织和除癌症以外的疾病中的作用在很大程度上被忽视了。在这篇综述中，我们总结了 PD-L1 在非癌细胞中的功能，概述了它的发现和起源，以及它在不同细胞和免疫相关过程中的参与。我们提供了 PD-L1 在不同细胞和器官中转录和翻译调节以及表达模式的概述，并阐明了 PD-L1 在不同自身免疫性疾病以及移植和妊娠背景下的参与情况。
