Table 1 Roles of IL-33 in brain neurological diseases
From: Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation
Diseases/models | IL-33/ST2 level | Mechanism | Function | References |
|---|---|---|---|---|
Damage | ||||
 AD and MCI patients | IL-33(↑) ST2(↑) | Higher levels of apolipoprotein E ε4 and phosphorylated tau are indeed associated with cognitive decline | Patients expressing IL-33 preserve their cognitive function | [66] |
 MS patients | IL-33(↑) | Inhibits CNS myelination | Involves in the pathogenesis of all MS | |
 EAE mice | IL-33(↑) ST2(↑) | Enhances Th1/Th17 response Inhibits Treg response | Promotes EAE | [113] |
 HIV-infected cells | IL-33(↑) ST2L(↑) | Leads to neuroinflammation Dys-regulates synaptic function and apoptosis | Promotes HIV | [135] |
 ECM | IL-33(↑) | Orchestrates an amplification loop between IL-1β and IL-33 in microglia and oligodendrocytes to exacerbate neuroinflammation | Exacerbates neurological and cognitive defects | [3] |
Protect | ||||
 TBI human and mice | IL-33(↑) | Promotes recruitment of microglia and release of pro-inflammatory mediators | Promotes TBI | [150] |
 APP/PS1 mice | IL-33(↑) sST2(↓) | Reverses synaptic plasticity impairment Promotes microglia polarization toward anti-inflammatory M2 Promotes microglia phagocytic activity to Aβ uptake | Ameliorates AD and cognitive decline | |
 EAE mice | IL-33(↑) ST2(↑) | Switches a predominantly pathogenic Th17/Th1 response to Th2 activity Promotes microglia polarization toward anti-inflammatory M2 Suppresses the activation of astrocytes and microglia | Attenuates EAE | |
 ECM | – | Reduces pro-inflammatory cytokine and chemokine Drives the expansion of ILC2 to produce Type-2 cytokines Leads to the polarization of the anti-inflammatory M2 and expands Treg | Prevents the development of ECM | [79] |
 RNS mice | IL-33(↓) ST2(↓) | Inhibits apoptosis, ER stress, and autophagy Reverses the up-regulation of IL-1β and TNF-α levels | Attenuates RNS-induced neurobehavioral disorders and spatial learning and memory deficits | |
 ICH mice/rats | IL-33(↓) ST2L(↑) | Suppresses the expression of pro-inflammation cytokines IL-1β and TNF-α Promotes microglia M2 polarization Suppresses apoptotic and autophagic activation | Alleviates ICH-induced neurological deficits, neuronal degeneration, cell death, and neurobehavioral deficits | |
 Stroke mice/MCAO mice | – | Inhibits Th1/Th17 response Enhances Treg response Induces immune-shift of Th cells from Th1 to Th2 response Promotes microglia polarization toward anti-inflammatory M2 | Provides neuroprotection | |
 TBI mice | IL-33(↑) ST2L(↓) | Inhibits autophagy, ERS, and apoptosis Prevented TBI-induced increase of IL-1β and TNF-α levels to inhibit neuroinflammation Promotes the polarization of M2 microglial and type-2 phenotype cytokines production | Mitigates TBI-induced motor function outcome, spatial learning, and memory deficits | |
 Stroke patients and mice models | IL-33(↑) sST2(↑) | Increases M2-type microglia and induces IL-4 secretion Reduces astrocytes activation | Reduces ischemia-induced sensorimotor deficits | [116] |