# Myeloid PD‐1 Regulates Astrocyte Development and Leads to Active Behaviours

## TL;DR

This study shows that removing PD-1 in myeloid cells disrupts brain development by causing astrocyte overgrowth and behavioral changes in mice.

## Contribution

The study reveals a novel regulatory role of myeloid PD-1 in astrocyte development and behavior through the NF-κB and CXCL1/CXCR2 pathways.

## Key findings

- PD-1 ablation in myeloid cells leads to sustained astrocyte proliferation.
- PD-1 deletion activates NF-κB, increasing CXCL1 and promoting astrocyte growth via CXCR2.
- Mice lacking PD-1 in myeloid cells show elevated astrocyte gene expression and extroverted behavior.

## 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‐1f/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.

During early neurodevelopment, PD‐1 ablation in myeloid cells influences myeloid proliferation/differentiation and causes sustained astrocyte overproliferation. PD‐1f/f; LysM‐Cre mice showed elevated astrocyte gene expression and behavioural changes. Mechanistically, PD‐1 deletion activates NF‐κB‐mediated CXCL1 secretion, driving astrocyte proliferation via CXCR2, revealing PD‐1's critical role in myeloid‐astrocyte crosstalk.