Immunosuppression mechanisms studied in stroke

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]
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.

Exp Neurobiol 2021;30:101~112
© Exp Neurobiol