The potential role of IL-33/ST2 signaling in fibrotic diseases

J Leukoc Biol. 2015 Jul;98(1):15-22. doi: 10.1189/jlb.3RU0115-012R. Epub 2015 Apr 16.

Abstract

IL-33, a new member of the IL-1F, is widely expressed throughout the body and can be up-regulated by stimulation with proinflammatory factors. It has been identified as a functional ligand for the plasma membrane receptor complex that is a heterodimer consisting of membrane-bound ST2L, which is a member of the IL-1R family, and IL-1RAcP. IL-33 is crucial for the induction of Th2 immune responses. Additionally, under other circumstances, it can also act as an endogenous danger signal. Recently, many studies have demonstrated that IL-33 may be related to the development and progression of fibrotic diseases. It has proinflammatory effects in some fibrotic diseases but has anti-inflammatory effects in others. In this review, the biologic characteristics of IL-33 and the role of the IL-33/ST2 signaling pathway in various fibrotic diseases will be discussed. We hope this overview will provide new insights for the treatment of these diseases.

Keywords: cardiac fibrosis; hepatic fibrosis; pulmonary fibrosis; skin fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Fibrosis / metabolism*
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / physiology*
  • Receptors, Cell Surface / physiology*
  • Receptors, Interleukin / metabolism
  • Signal Transduction / physiology*

Substances

  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Receptors, Cell Surface
  • Receptors, Interleukin