Effects of Pd1 targeted myeloid deletion on brain development

During early brain development, the nervous system continues to evolve and improve, and cells in different stages contact and connect to form a unique nervous system network. Various cross-talk between cell populations is the key to neurological homeostasis. Communication between astrocytes and myeloid cells affects brain function. Programmed cell death protein 1 (PDCD1), also known as PD-1 or CD279 (differentiation cluster 279), is a member of the immunoglobulin gene superfamily. Here, we investigated the loss of PD-1 in myeloid cells results in abnormal development of the nervous system. Specific ablation of PD-1 affects myeloid cell proliferation and subtype classification. At the stage of astrogenesis onset, the astrocyte proliferation ends, and the continuous development, the results of immunofluorescence staining with different astrocyte markers show that astrocytes-related genes were highly expressed in PD-1f/flysMCre mice. PD-1f/flysMCre mice exhibited more outgoing, less anxious, and a more extroverted mode of exploration in behavioral tests. The specific ablation of PD-1 increases the expression of CXCL1 through the NF-κB signaling pathway. It reaches the brain and interacts with CXCR2 on astrocytes, promoting astrocyte proliferation. Our results not only reveal an important regulatory role of PD-1 in myeloid cells on astrocytes but also provide some theoretical basis and ideas for the study of myeloid and brain axis