CD204 regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a main cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key events following ICH, but the molecular mechanisms of mediator regulatory function are not well understood. Cluster of differentiation 204 (CD204), a macrophage scavenger receptor, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in ICH has not been addressed. In the current study, we aimed to investigate whether CD204 is involved in the regulation of M1/M2 microglial/macrophage polarization and neuroinflammation following ICH. The ICH mouse model was employed. CD204 siRNA was intracerebroventricularly administered, and tamibarotene was intraperitoneally administered for intervention. The neurobehavioral assessments, RT-PCR, Western blot, immunohistochemistry, Nissl staining, and ELISA were performed. CD204 is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in ICH. Mechanistically, inhibition of CD204 markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the brain injury after ICH. Tamibarotene exerts beneficial effects in ICH mice through CD204 activation. CD204 plays an important role in M1/M2-macrophage/microglial polarization, providing novel potential therapeutic targets for the regulation of immune and inflammatory disorders in ICH.