Targeting CD74 in microglia to modulate experimental cerebral ischemia and reperfusion injury: insights from Single-Cell and bulk transcriptomics

作者：Chang Cao, Ting Liu, Peng Lü, Lianxin Li, Zhongmou Xu, Xiangyang Li, Gang Chen, Haiying Li, Lei Bai · 发表于：Molecular Brain · 年份：2025 · DOI：10.1186/s13041-025-01197-8 · 被引用次数：7 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Immune cells in cancer、Neurological Disease Mechanisms and Treatments

Ischemic stroke remains a leading cause of mortality and long-term disability, with reperfusion injury contributing significantly to poor clinical outcomes. Microglia, the primary immune cells of the central nervous system, play a dual role in ischemic stroke by both exacerbating injury through neuroinflammation and supporting recovery through neuroprotection. This study aimed to explore the role of CD74, a gene upregulated in microglia following ischemia-reperfusion injury. Using single-cell RNA sequencing and bulk RNA sequencing, we identified CD74 as a potential target involved in microglial-mediated neuroinflammation. We observed a significant increase in CD74 expression in microglia following middle cerebral artery occlusion/reperfusion (MCAO/R), which correlated with pro-inflammatory cytokine production and neuroinflammation. Targeted knockdown of CD74 in microglia using CX3CR1Cre/ERT2 mice led to a reduction in infarct volume, inflammatory cytokine levels, and long-term neurological deficits. Behavioral tests showed improved motor coordination, sensory function, and exploratory behavior in CD74 knockdown mice. These results suggest that CD74 is a critical mediator of microglia-driven neuroinflammation, and targeting CD74 may represent a promising therapeutic strategy for reducing ischemic brain injury and promoting recovery after stroke.