CCL17/CCR4 Axis Promotes Hematoma Clearance via ERK/AP1/SRA‐Mediated Microglial Polarization After Intracerebral Hemorrhage

• DOI: 10.1111/cns.70288
• Publication Date: 2025-03-03T11:47:40Z
• Authors: Xianglan Chen; Yao Wang; Junjie Jin; Peng Jin; Shuixiang Deng
• Keywords: CCL17; CCR4

Our previous studies demonstrated that CCL17 and its receptor CCR4 play crucial roles in neuroinflammation microglial activation following intracerebral hemorrhage (ICH). However, the specific mechanisms by which CCL17/CCR4 axis regulates polarization hematoma clearance remain unclear. This study investigates how signaling pathway modulates phenotype transition enhances resolution after ICH, building upon our earlier findings showing CCR4's involvement neuroinflammatory responses. Using CRISPR-mediated disruption overexpression approaches a mouse ICH model, we examined neurological outcomes, inflammatory responses, volumes. We further evaluated therapeutic potential of recombinant administration. The downstream ERK pathway's role CCL17/CCR4-mediated function was investigated through pharmacological inhibition. knockout exacerbated deficits, increased neuroinflammation, enlarged hematomas. In contrast, enhancing expression or administering improved functional recovery provided neuroprotection. Mechanistically, activated ERK/AP1/SRA pathway, promoting anti-inflammatory, phagocytic polarization, evidenced CD206 SRA expression. inhibition reversed these protective effects. extend work revealing pathway-mediated polarization. mechanism represents promising target for treatment.