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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]