Table 1.
Expression and mechanisms of IL-33/ST2 in rheumatic diseases.
| Disease | Role of IL-33/ST2 in disease pathogenesis | Referencess |
|---|---|---|
| SLE | IL-33 and sST2 levels were increased in the serum of SLE patients. IL-33 neutralization had a protective effect in MRL/lpr mice, which was associated with the increase of regulatory T cells and myeloid-derived suppressor cells and the reduction of Th17 cells and pro-inflammatory factors. IL-33 might be involved in innate lymphoid cell disorder in the peripheral blood of SLE patients. |
(61–64) |
| RA | IL-33 levels were related to the severity and activity of RA. IL-33 enhanced TNF-α-dependent effects in synovial fibroblasts. ST2−/− and ST2 neutralization in the CIA model alleviated arthritis symptoms, while administration of IL-33 exacerbated. IL-33 stimulates mast cells to produce pro-inflammatory factors. IL-33 stimulated macrophages and synovial cells to produce chemokines, which recruited neutrophils. |
(65–71) |
| pSS | IL-33 and sST2 levels were increased in the serum of pSS patients. IL-33 promoted the release of IFN-γ in NK and NKT cells when combined with IL-12 and/or IL-23. |
(72–74) |
| SSc | IL-33 and sST2 levels were increased in the serum of SSc patients. IL-33 levels were correlated with skin lesions, degree of sclerosis. IL-33 polarized M2 macrophages to produce TGF-β1 and IL-13, induced ILC2 proliferation, increased eosinophils and the level of IL-13, and induced Treg dysfunction. |
(75–79) |
| PsA | IL-33 levels were increased in the serum of patients. IL-33 increased the gene expression of the pro-osteoclastogenic factor associated with bone damage. |
(80, 81) |
| Gout | IL-33 levels were increased in joint synovial fluid. Exogenous administration of IL-33 aggravated the production of ROS and recruitment of neutrophils, while knocking out ST2 alleviated the oxidative stress and neutrophils recruitment. IL-33 stimulated macrophages to produce CXCL1, CCL 3, and IL-1β. IL-33 recruited bone marrow-derived suppressor cells and reduced the production of IL-1β. |
(82–84) |
| IgG4-RD | IL-33 levels were increased in the serum of patients. Prednisolone treatment decreased the serum concentration of IL-33. IL-33 activated the Th2 immune response and promoted tissue fibrosis. |
(85–87) |
| AS | Serum IL-33 levels were elevated in the patients with AS. IL-33 enhanced the production of TNF-α and IL-6 in peripheral blood mononuclear cells and induced neutrophil migration. IL-33 was used as a predictor of the therapeutic effect of infliximab in the treatment of AS. |
(88–91) |
| IIM | Serum sST2 levels were elevated and correlated with CRP, CK, and LDH. | (92, 93) |
| AOSD | Serum IL-33 and sST2 levels were elevated and correlated with ferritin levels. | (94) |
| BD | Serum and skin tissue of IL-33 and sST2 levels were elevated in patients. | (95, 96) |
SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; CIA, collagen-induced arthritis; pSS, primary Sjögren's syndrome; NK, natural killer cells; NKT, natural killer T cells; SSc, systemic sclerosis; PsA, psoriatic arthritis; ROS, reactive oxygen species; IgG4-RD, IgG4-related disease; AS, ankylosing spondylitis; IIM, idiopathic inflammatory myopathies; CRP, C-reactive protein; CK, creatine kinase; LDH, lactate dehydrogenase; AOSD, adult-onset Still's disease; BD, Behcet's disease.