Emerging role of the interleukin (IL)-33/ST2 axis in gut mucosal wound healing and fibrosis

Lopetuso, Loris R; Scaldaferri, Franco; Pizarro, Theresa T

doi:10.1186/1755-1536-5-18

Fibrogenesis & Tissue Repair

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]

Back to article page

ISSN: 1755-1536

Contact us

General enquiries: info@biomedcentral.com