Yanyan Wang, Mengtian Zhang, Tianyu Zhang, Shukui Zhang, Fen Ji, Jie Qin, Hong Li, Jianwei Jiao
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引用次数: 0
Abstract
Programmed cell death protein 1 (PD-1) and its primary ligand PD-L1 are integral components of a significant immune checkpoint pathway, widely recognized for its central role in cancer immunotherapy. However, emerging evidence highlights their broader involvement in both the central and peripheral nervous systems. In this study, we demonstrate that PD-L1/PD-1 signaling in astrocytes during mouse brain development regulates astrocyte maturation and morphogenesis via the MEK/ERK pathway by targeting the downstream effector cysteine and glycine rich protein 1 (CSRP1). This enhanced astrocyte morphological complexity results in increased end-foot coverage of blood vessels. Additionally, aberrant secretion of CSRP1 by astrocytes interacts with oligodendrocyte precursor cells (OPCs) membrane proteins annexin A1 (ANXA1) and annexin A2 (ANXA2), leading to the exclusion of migrating OPCs from blood vessels. This disruption in OPC migration and differentiation results in abnormal myelination and is associated with cognitive deficits in the mice. Our results provide critical insights into the function of PD-L1/PD-1 signaling in astrocyte-OPC interactions and underscore its relevance to glial cell development and pathogenesis in neurodevelopmental disorders.
期刊介绍:
Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.