Table 2.
Effects of endogenous and exogenous IL-33 in AKI models.
| Animals | Model | Key Findings | Reference |
| Endogenous IL-33 | |||
| IL33 Gt/Gt | IRI | Capillary CD31+ endothelial cells are the source of IL-33 | Ferhat et al. [62] |
| IL-33 knockout is protective to IRI | |||
| Reduced myeloid cell infiltration in IL-33 knockout mice | |||
| Impaired iNKT recruitment and function in the IL-33 knockout mice | |||
| Early IL-33 release (1–6 h post injury) is not necessary for myeloid recruitment after IRI | |||
| IL-33-mediated iNKT activation contributes to neutrophil recruitment during the amplification phase of kidney injury | |||
| Exogenous IL-33 treatment | |||
| mouse IL-33 (0.3 μg/mice for 5 days); C57BL/6 | IRI | Exogenous IL-33 protects mice against IRI (pre-treatment or post-treatment) | Cao et al. [49] |
| Exogenous IL-33 decreased GR-1+ myeloid cells post-IRI | |||
| Exogenous IL-33 induced Th2 cytokines, ILC2s, Tregs, and AAMs in vivo | |||
| IL-33 boosts kidney-resident ILC2 proliferation in vivo | |||
| Treg did not contribute to IL-33-mediated renoprotection in IRI mice | |||
| GW2580-mediated AAM depletion abolished IL-33-mediated renoprotection in IRI mice | |||
| Anti-CD90-mediated ILC depletion abolished IL-33-mediated renoprotection in IRI mice | |||
| Adoptive transfer of ILC2 protects mice from IRI | |||
| AREG mediates renoprotective function of ILC2s | |||
| IL-33 and ILC2s are protective post-IRI | |||
| mouse IL233 (66pmol /mice for 5 days); C57BL/6J and Balb/cJ | IRI Doxorubicin Cisplatin | Exogenous IL-2 combined with IL-33 (IL233) is protective post-IRI | Stremska et al. [51]; Sabapathy et al. [50] |
| IL233 promotes the expansion of ILC2s and Tregs, which is required for the renal protective functions | |||
| IL233 is renal protective in IRI-, cisplatin-, and doxorubicin-induced nephrotoxicity | |||
| mouse IL-33 | IRI | Exogenous IL-33 promotes IRI-induced fibrosis | Liang et al. [53] |
| sST2 attenuates IRI-induced renal injury and fibrosis | |||
| mouse IL-33 (0.4μg/mice for 4 days); C57BL/6 and Balb/c | Adriamycin (Doxorubicin) | ST2+ILC2s are the major ILC2 population in human and mouse kidneys | Riedel et al. [48] |
| Exogenous IL-33 induces sustained ILC2 expansion in the kidneys | |||
| Exogenous IL-33 ameliorates Adrimycin-induced kidney injury | |||
| Eosinophils are required for IL-33-mediated tissue protection | |||
AKI, acute kidney injury; IRI, ischemia-reperfusion injury; ILC2, group 2 innate lymphoid cells, AAM, alternative activated macrophages; iNKT, invariant nature killer T-cells; sST2, soluble ST2.