Table 1.

The role of IL-33/ST2 in fibrosis of various organs.

Fibrotic organ	Disease	Findings	References
Respiratory fibrosis	Asthma	Knockdown of ST2 reduces IL-33-induced collagen I, III, and fibronectin expression, thereby reducing ECMs deposition	An et al., 2018
	Idiopathic pulmonary fibrosis	The levels of ST2, MyD88, and TRAF6 proteins in bleomycin-induced pulmonary fibrosis tissues were elevated.	Xu et al., 2016
	Pulmonary inflammation	IL-33 promotes initiation and progression of pulmonary fibrosis by M2-like polarization of macrophages through ST2 signaling.	Fanny et al., 2018
Cardiac fibrosis	Cardiomyocyte hypertrophy	IL-33 is mechanically induced in cardiac fibroblasts and antagonizes hypertrophic stimuli. IL-33 blocks NF-κB activation by angiotensin II and phenylephrine.	Sanada et al., 2007
	Myocardial infarction	IL-33 aggravated the deterioration of cardiac function, which is associated with activated myofibroblasts and a increase in pro-fibrotic markers, such as connective tissue growth factor (CTGF), and TGF-β.	Ghali et al., 2020
Intestinal fibrosis	Crohn’s disease	IL-33/ST2 pathway may lead to upregulation of TGF-β and facilitate collagen deposition in fibroblasts.	Imai et al., 2019
Liver fibrosis	Chronic CCL4 dependent hepatic fibrosis	IL-33 is released in response to chronic hepatocellular stress. And extracellular IL-33, leads to accumulation and activation of ILC2 in the liver via ST2-dependent signaling. Activated hepatic ILC2 produce IL-13, which in turn triggers activation and trans-differentiation of hepatic stellate cells (HSCs).	Marvie et al., 2010
	Biliary atresia (BA)	IL-33/ST2 pathway is correlated with liver fibrosis progression in BA patients, and mast cells participate in this process.	Liu et al., 2019b
	Hepatic inflammation	IL-33/ST2 pathway may activate HSCs via MEK/ERK/p38-MAPK signaling.	Tan et al., 2018
Cutaneous fibrosis	Skin inflammation	IL-33 induced fibrosis in an IL-13–dependent manner. And, IL-33 induced skin fibrosis is dependent on eosinophils.	Rankin et al., 2010