IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages
- 3 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Differentiation
- Vol. 28 (4), 1270-1283
- https://doi.org/10.1038/s41418-020-00650-6
Abstract
Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and has one of the poorest prognosis. However, the molecular mechanisms underlying IPF progression remain largely unknown. In this study, we determined that IL-24, an IL-20 subfamily cytokine member, was increased both in the serum of IPF patients and the bronchoalveolar lavage fluid (BALF) of mice following bleomycin (BLM)-induced pulmonary fibrosis. As a result, IL-24 deficiency protected mice from BLM-induced lung injury and fibrosis. Specifically, loss of IL-24 significantly attenuated transforming growth factor β1 (TGF-β1) production and reduced M2 macrophage infiltration in the lung of BLM-induced mice. Mechanistically, IL-24 alone did not show a perceptible impact on the induction of M2 macrophages, but it synergized with IL-4 to promote M2 program in macrophages. IL-24 suppressed IL-4-induced expression of suppressor of cytokine signaling 1 (SOCS1) and SOCS3, through which it enhanced signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma (STAT6/PPARγ) signaling, thereby promoting IL-4-induced production of M2 macrophages. Collectively, our data support that IL-24 synergizes with IL-4 to promote macrophage M2 program contributing to the development of pulmonary fibrosis.Keywords
Funding Information
- National Natural Science Foundation of China (81530024)
This publication has 48 references indexed in Scilit:
- IL-22 Promotes Fibroblast-Mediated Wound Repair in the SkinJournal of Investigative Dermatology, 2013
- Regulation of TGF-β storage and activation in the human idiopathic pulmonary fibrosis lungCell and tissue research, 2012
- An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and ManagementAmerican Journal of Respiratory and Critical Care Medicine, 2011
- IL‐24 is expressed during wound repair and inhibits TGFα‐induced migration and proliferation of keratinocytesExperimental Dermatology, 2010
- Alternative Activation of Macrophages: Mechanism and FunctionsImmunity, 2010
- IL-4 alters expression patterns of storage components of vascular endothelial cell-specific granules through STAT6- and SOCS-1-dependent mechanismsMolecular Immunology, 2009
- Protein kinase C δ is essential for optimal macrophage-mediated phagosomal containment ofListeria monocytogenesProceedings of the National Academy of Sciences of the United States of America, 2007
- Macrophage-specific PPARγ controls alternative activation and improves insulin resistanceNature, 2007
- Cytokine induction of interleukin-24 in human peripheral blood mononuclear cellsJournal of Leukocyte Biology, 2005
- Interleukin‐24 and its receptorsImmunology, 2005