Myeloid PD-1 Regulates Astrocyte Development and Leads to Active Behaviours

Abstract

During early brain development, the nervous system evolves as cells connect to form a unique neural network, with communication between cell populations vital for neurological balance. This study investigates how the loss of PD-1 in myeloid cells disrupts nervous system development. Specific ablation of PD-1 affects myeloid cell proliferation and classification. As astrogenesis begins, astrocyte proliferation ceases, continuous astrocyte proliferation is observed. Immunofluorescence staining revealed high expression of astrocyte-related genes in PD-1^{f/f; LysM-Cre} mice, which also exhibited more extroverted behaviour. Additionally, the absence of PD-1 enhances CXCL1 expression through the NF-κB pathway, promoting astrocyte proliferation by interacting with CXCR2. These findings underscore PD-1's regulatory role in myeloid cells and its implications for the myeloid-brain axis.

Keywords

astrocyte / myeloid cell / neural stem cells (NSCs) / PD-1 / proliferation and differentiation

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2025 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.