Neutralizing XCL1 Attenuates Brain Injury and Reduces Lymphocyte and Dendritic Cell Recruitment Following...

The interaction between chemokine-C-motif ligand 1 (XCL1) and X-C motif chemokine receptor 1 (XCR1), members of the CXC chemokine family, amplifies immune-inflammatory responses via lymphocyte activation. The influence of lymphocyte infiltration on stroke outcome underscores the importance of investigating the potential role of the XCL1-XCR1 axis in stroke pathophysiology. In this investigation, we examined the expression of XCL1 and XCR1 in the hemorrhagic brain in mice subjected to Ⅶ-S collagenase-induced intracerebral hemorrhage (ICH) in the left striatum. We also evaluated the efficacy of the XCL1-XCR1 axis on neuroinflammation and ICH outcomes by neutralizing XCL1. The results unveiled that infiltrating immunocytes and microglia manifest XCL1 immunoreactivity and that XCR1-positive cells co-express distinct markers of glia and neurons within the hemorrhagic brain. Notably, a decrease in the infiltration of helper T cells, cytotoxic T cells, natural killer cells, dendritic cells (DCs), and XCR1⁺ DCs in the hemorrhagic brain was observed 3 days post-ICH following the administration of the XCL1 neutralizing antibody. Furthermore, a reduction in glial activation, neutrophil infiltration, and the production of proinflammatory cytokines was evident early after ICH. The observed mitigation of brain damage and neurological impairments over the 28-day study period suggests potential therapeutic benefits stemming from these identified changes. According to this study, treatment with an XCL1-neutralizing antibody is linked to decreased lymphocyte/DC recruitment, reduced neuroinflammation, and better functional outcomes in mice after ICH. Hence, exploring the XCL1-XCR1 axis to diminish the recruitment of peripheral immune cells and promote neuroprotection following ICH warrants further investigation.