1. Nat. Rev. Neurol. doi:10.1038/nrneurol.2017.69
Figure 2 Modulators of microglial polarization and phagocytosis after intracerebral haemorrhage.
Figure 2 | Modulators of microglial polarization and phagocytosis after intracerebral haemorrhage. Several transcription factors modulate microglial polarization towards an M1-like (left panel) or an M2-like (centre panel) phenotype. Activation of high-mobility group protein 1 (HMG1) and Toll-like receptor (TLR)2 or TLR4 promotes microglial M1-like responses. Signal transducer and activator of transcription (STAT)1 is activated by TLRs and IFNγ, promoting microglial polarization to an M1 phenotype. After intracerebral haemorrhage (ICH), TLRs modulate STAT3 phosphorylation, which increases M1-like polarization. G-protein-coupled E prostanoid (EP) receptors EP1 and EP3 are mainly expressed on microglia and drive neuronal toxicity mediated by M1 upregulation after ICH. STAT6 accumulates in response to IL-4 and is responsible for the transcription of M2-related genes. Sphingosine-1-phosphate (S1P) receptor signalling contributes to the downregulation of proinflammatory cytokines and enhances M2-like responses after ICH. Although EP2 receptors are not expressed in microglia after ICH, EP2 deletion results in an increased microglial proinflammatory response. Other modulators regulate microglial phagocytosis (right panel). Activation of the transcription factor nuclear factor erythroid 2- related factor 2 (Nrf2) is associated with microglial phagocytosis after ICH and increases CD36 and haem oxygenase-1 (HO-1) expression. The CD36 gene is a target of peroxisome proliferator-activated receptor-γ (PPARγ), which belongs to the nuclear receptor family. CD47 expression in red blood cells (RBC) can decrease their phagocytosis by microglia after ICH. Although CD36 expression is increased in the ICH brain, TLR4 activation might negatively regulate its expression and delay haematoma clearance. IFGNR, IFNγ receptor; NF-κB, nuclear factor-κB; MAL, Toll/IL-1 receptor domain-containing adaptor protein (also known as MYD88 adapter-like protein); MYD88, myeloid differentiation primary response protein MYD88; SOCS3, suppressor of cytokine signalling 3; TRAM, TIR domain-containing adaptor molecule 2 (also known as TRIF-related adaptor molecule); TRIF, TIR domain-containing adaptor molecule 1.
Lan, X. et al. (2017) Modulators of microglial activation and polarization after intracerebral haemorrhage
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