CSF1R blockade slows progression of cerebral hemorrhage by reducing microglial proliferation and increasing infiltration of CD8 + CD122+ T cells into the brain

• DOI: 10.1016/j.intimp.2024.112071
• Publication Date: 2024-04-17T04:05:20Z
• Authors: Fangyuan Cheng; Conglin Wang; Bo Yan; Zhenyu Yin; Yaru Liu; Lan Zhang; Meimei Li; Pan Liao; Han Gao; Zexi Jia; Dai Li; Qiang Liu; Ping Lei
• Keywords: Male; Receptors, CXCR3; Brain; Anisoles; CD8-Positive T-Lymphocytes; Interleukin-10; Chemokine CXCL10; Interleukin-2 Receptor beta Subunit; Mice, Inbred C57BL; Mice; Disease Models, Animal; Pyrimidines; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Animals; Microglia; Cell Proliferation; Cerebral Hemorrhage

Microglia play a pivotal role in the neuroinflammatory response after brain injury, and their proliferation is dependent on colony-stimulating factors. In the present study, we investigated the effect of inhibiting microglia proliferation on neurological damage post intracerebral hemorrhage (ICH) in a mouse model, an aspect that has never been studied before. Using a colony-stimulating factor-1 receptor antagonist (GW2580), we observed that inhibition of microglia proliferation significantly ameliorated neurobehavioral deficits, attenuated cerebral edema, and reduced hematoma volume after ICH. This intervention was associated with a decrease in pro-inflammatory factors in microglia and an increased infiltration of peripheral regulatory CD8 + CD122+ T cells into the injured brain tissue. The CXCR3/CXCL10 axis is the mechanism of brain homing of regulatory CD8 + CD122+ T cells, and the high expression of IL-10 is the hallmark of their synergistic anti-inflammatory effect with microglia. And activated astrocytes around the insult site are a prominent source of CXCL10. Thus, inhibition of microglial proliferation offers a new perspective for clinical translation. The cross-talk between multiple cells involved in the regulation of the inflammatory response highlights the comprehensive nature of neuroimmunomodulation.