TABLE 1.
Potential immunotherapeutic targets on myeloid cells for NVU repair after stroke.
| Cellular targets | Functions and underlying mechanisms | References |
| Msr1 | Clearance of DAMPs; reduce the expression of inflammatory cytokines | Shichita et al., 2017 |
| CD36 | Clearance of cell debris; attenuation of nuclear factor-κB mediated inflammation; | Cho et al., 2005; Woo et al., 2012 |
| TREM2 | Promotes microglial survival by inhibiting β-catenin degradation via the Akt/GSK3β signaling pathway; phagocytosis apoptotic neurons, amyloid plaques and anionic and zwitterionic lipids on damaged neurons | Hsieh et al., 2009; Wang et al., 2015; Yuan et al., 2016; Zheng et al., 2017 |
| CR1 | Induction of phagocytosis by interacting with its ligands; clearing debris, apoptotic or necrotic neurons and limiting neuroinflammation | Rotshenker, 2003; Fourgeaud and Boulanger, 2007 |
| MRs | Enhance the clearance ability of microglia/macrophages | Giraldi-Guimaraes et al., 2012 |
| MerTK | Phagocytosis of ischemic neurons; clearance of hetatoma and reduce iron deposition | Neher et al., 2013; Chang et al., 2018 |
| arginase-1, CD206, Ym1 and TGF β and IL-10 | Induce the anti-inflammatory effect of microglia and macrophages by activating CX3CL1-CX3CR1 signaling, IL-33/ST2 signaling and neuronal IL-4, PPARγ | Mizuno et al., 2003; Lyons et al., 2009; Zhao et al., 2015; Liu X. et al., 2016; Yang et al., 2017 |
| PPARγ in N2 neutrophils | Limit excessive immune response, promoting neuronal survival and successful brain remodeling after ischemic stroke and ICH | Hermann et al., 2018 |
| lactoferrin | Iron-scavenging and clearance of hetatoma | Zhao X. et al., 2017 |
| IGF-1 | Promote proliferation and differentiation of NSCs | Thored et al., 2009 |
| BDNF | Regulate synaptic function and promote multiple learning tasks performance | Coull et al., 2005 |
| IL-8, VEGF, TGF-β, prostaglandin, MMP-9 | Enhance the angiogenic process | Sanberg et al., 2010 |
| Filopodia or lamellipodia | Physically adhere to both endothelial ends at the cerebral vascular rupture lesion | Liu C. et al., 2016 |
| iron-releasing phenotype of microglia | Promoting oligodendrocyte progenitor cell differentiation | Shin et al., 2018 |
| EVs, exosomes, miRNA124-3p | Inhibit neuronal inflammation and promote neurite outgrowth | Ponomarev et al., 2013; Huang et al., 2018 |
NVU, neurovascular unit; Msr1, macrophage scavenger receptor 1; DAMP, damage associated molecular patterns; CD36, cluster of differentiation 36; TREM2, triggering receptor expressed on myeloid cells-2; CR, complement receptor; MR, mannose receptor; MerTK, mer receptor tyrosine kinase; PPARγ, peroxisome proliferator-activated receptor γ; CX3CL1-CX3CR1, chemokine (C-X3-C motif) ligand 1-CX3C chemokine receptor 1; IL-33, interleukin 33; IL-4, interleukin 4; ICH, intracerebral hemorrhage; IGF-1, insulin-like growth factor-1; NSC, neural stem cell; BDNF, brain-derived neurotrophic factor; IL-8, interleukin 8; VEGF, vascular endothelial growth factor; TGF-β, transforming growth factor β; MMP-9, matrix metallopeptidase 9; EVs, extracellular vesicles.