IL-25/IL-33/TSLP contributes to idiopathic pulmonary fibrosis: Do alveolar epithelial cells and (myo)fibroblasts matter?

Exp Biol Med (Maywood). 2020 May;245(10):897-901. doi: 10.1177/1535370220915428. Epub 2020 Apr 4.

Abstract

We suggest a novel modality in terms of IL-25/IL-33/TSLP's pro-fibrotic role in IPF. First, IL-25/IL-33/TSLP fully activates (myo)fibroblasts in fibroblastic foci (FF) in a paracrine-dependent manner. (IL-25/IL-33/TSLP)+alveolar epithelial cells-(IL-25R/IL-33R/TSLPR)+ (myo)fibroblasts axis may contribute greatly to the abnormal epithelial-mesenchymal crosstalk and lung fibrosis. Second, IL-25/IL-33/TSLP causes significant injury and phenotypic changes of alveolar epithelial cells in an autocrine-dependent manner. By acting directly on the two most important cells in the fibrotic process, i.e. alveolar epithelial cells and (myo)fibroblasts, we support the notion that biological therapies targeting IL-25/IL-33/TSLP will shed new light on the cure of IPF patients.

Keywords: Epithelial-mesenchymal crosstalk; IL-25/IL-33/TSLP; fibroblastic foci; idiopathic pulmonary fibrosis.

Publication types

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

MeSH terms

  • Alveolar Epithelial Cells / immunology
  • Alveolar Epithelial Cells / metabolism
  • Alveolar Epithelial Cells / pathology*
  • Animals
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Humans
  • Idiopathic Pulmonary Fibrosis / immunology
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Interleukin-33 / immunology
  • Interleukin-33 / metabolism*
  • Myofibroblasts / immunology
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology*
  • Signal Transduction / immunology
  • Thymic Stromal Lymphopoietin

Substances

  • Cytokines
  • IL25 protein, human
  • Interleukin-17
  • Interleukin-33
  • Thymic Stromal Lymphopoietin