Table 1.
Roles of IL-33 in brain neurological diseases
| 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 | [8, 118, 147, 148] |
| 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 | [47, 80] |
| 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 | [78, 84, 112] |
| 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 | [28, 85] |
| 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 | [87, 88] |
| 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 | [90, 100, 115] |
| 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 | [86, 91] |
| 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] |