Immunosuppression mechanisms studied in stroke
| References | ||
|---|---|---|
| Innate immune system | ||
| TAM/Gas6 | rGas6 reduced brain injury via inhibition of the TLR/TRAF/NF-κB pathway | [39] |
| Anti-inflammatory mediators | ||
| IL-1 receptor antagonist | IL-1Ra has been used safely for ischemic stroke in Phase II trials | [55] |
| IL-1Ra promotes neuroprotection | [20] | |
| IL-10 | IL-10 promotes neuronal survival and inhibits inflammatory responses | [57] |
| IL-10−/− mice have increased infarct volumes 24 h after stroke | [61] | |
| TGF-β | TGF-β knockout aggravates brain damage | [68] |
| TGF-β overexpression decreases the inflammatory response and reduces brain injury in mice subjected to MCAO | [69] | |
| Adaptive immune system | ||
| Regulatory T cells (Tregs) | CD4+CD25+Tregs may be beneficial to neuronal survival | [88] |
| CD4+CD25+Tregs could facilitate cocaine-and-amphetamine-regulated-transcript-mediated neuroprotection after stroke | [89] | |
| Increased CD4+CD25+FoxP3+Tregs in the peripheral blood reduced T cell proliferation in patients with acute ischemic stroke | [90] | |
| Tregs reduced brain damage after ischemic stroke by mediating PD-1/PD-L1 interaction | [95] | |
| Neuro-immunomodulation | ||
| HPA axis | The HPA axis participates in negative neurohormonal regulation | [98] |
| SNS | The SNS regulates the inflammatory response | [100] |
| Cholinergic anti-inflammatory pathway | The cholinergic anti-inflammatory pathway inhibits the release of cytokines and promotes neuroprotection | [105] |
| α7 nAChRs | Treatment with the selective α7 nAChR agonist PHA 568487 was found to be associated with a decrease in the number of microglia expressing the M1 phenotype in a pMCAO model | [109] |
TLR, Toll-like receptor; TAM, Tyro3/Axl/MerTK; DAMP, Damage associated molecular pattern; Gas6, Growth arrest-specific 6; SOCS 1, Suppressor of cytokine signaling 1; SAH, Subarachnoid hemorrhage; Hsp70, Heat shock protein 70; IL-10, Interleukin-10; TGF-β, Transforming growth factor β; CSF, Cerebrospinal fluid; BBB, Blood brain barrier; SNS, Sympathetic nervous system; HPA, Hypothalamopituitary-adrenal; LRRs, Leucine-rich repeats; TIR, Toll/IL-1 receptor; MyD88, Myeloid differentiation protein 88; TRIF, TIR domain-containing adaptor inducing interferon β; NF-κB, Nuclear factor kappa B; LPS, Lipopolysaccharide; MCAO, Middle cerebral artery occlusion; IL-1, Interleukin-1; IL-1Ra, Interleukin-1 receptor antagonist; Tregs, Regulatory T cells; PD-1, Programmed death 1; MMP-9, Matrix metalloproteinase 9; DC, Dendritic cell; Th3, T helper 3 cell; Trl, Type 1 regulatory T cell; TNF-α, Tumor necrosis factor alpha.