Table 1 Role of IL-33/ST2 axis in animal models of tissue repair and fibrosis
From: Emerging role of the interleukin (IL)-33/ST2 axis in gut mucosal wound healing and fibrosis
| Target Organ/ System | Animal Model | Model Manipulation | Proposed Role of IL- 33 / ST2 | Postulated Mechanism |
|---|---|---|---|---|
| Intestine | ||||
| Chemically-induced barrier disruption, follwed by intestinal inflammation | Acute DSS colitis | Genetic deletion of IL-33 | Pathogenic | Neutrophil recruitment[42] |
| Exogenous IL-33 administration | Pathogenic | Neutrophil recruitment[43, 44] | ||
| Chronic DSS colitis | Exogenous IL-33 administration during recovery phase | Protective | Th1→Th2 switch: improvement of bacterial clearance[44] | |
| Chemically-induced ThI- mediated intestinal inflammation | TNBS colitis | Exogenous IL-33 administration | Protective | Th1→Th2 switch: expansion of Treg population[45] |
| Spontaneous, chronic intestinal inflammation | SAMP1/YitFc mice | Blockade of IL-33 by anti-ST2 antibody administration | Pathogenic | Activation of pathogenic IL-17-producing macrophages |
| Blockade of IL-33 by anti ST2 antibody administration | Pathogenic | Induction of Th2 cytokines; infiltration and activation of pathogenic eosinophils | ||
| Spontaneous, intestinal fibrosis | SAMP1/YitFc mice | Blockade of IL-33 by anti ST2 antibody administration | Pathogenic | Induction of Th2 cytokines; increased pro-fibrotic gene expression |
| Liver | ||||
| Chemically-induced liver fibrosis | Carbon tetrachloride liver intoxication | Exogenous IL-33 administration | Pathogenic | Th1→Th2 switch; pro-fibrogenic cytokine production[46] |
| Heart | ||||
| Mechanically-induced cardiac hypertrophy and fibrosis | Pressure overload by transverse aortic constriction | Interruption of IL-33 signaling by genetic deletion of ST2 | Protective | Regulation of NF-kB activation; reduction of macrophage infiltration; Inhibition of angiotensin II and phenylephrine-induced cardiomyocyte hypertrophy[27] |
| Lung | ||||
| Antitumor antibiotic-induced lung fibrosis | Bleomycin-induced lung fibrosis | Blockade of IL-33 by sST2 administration | Pathogenic | Th1→Th2 switch[28] |
| Joints | ||||
| Rheumatoid arthritis phenotype | Collagen-induced arthritis | Interruption of IL-33 signaling by genetic deletion of ST2 Exogenous IL-33 administration Bone marrow-derived mast cell adoptive transfer | Pathogenic | Activation of pathogenic mast cell[18] |
| Blockade of IL-33 by anti-ST2 antibody administration | Pathogenic | Induction of IFNγ and IL-17[17] | ||
| Skin | ||||
| Skin fibrosis | BL/6 mice | Exogenous IL-33 administration | Pathogenic | Accumulation of eosinophils, CD3+lymphocytes, F4/80+ mononuclear cells; increased IL-13 mRNA expression[47] |