Cited by 164Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisTransplantation: Methods and OutcomesCardiac Fibrosis and Remodeling

IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages

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Rao, Li-Zong, Wang, Yi, Zhang, Lei, Wu, Guorao, Zhang, Lu, Wang, Fa-Xi, Chen, Long-Min, Sun, Fei +14 more·2021·Cell Death & Differentiation

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.

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Crossref · 10.1038/s41418-020-00650-6

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Authors
Rao, L.-Z., Wang, Y., Zhang, L., Wu, G., Zhang, L., Wang, F.-X., Chen, L.-M., Sun, F., Jia, S., Zhang, S., Yu, Q., Wei, J.-H., Lei, H.-R., Yuan, T., Li, J., Huang, X., Cheng, B., Zhao, J., Xu, Y., Mo, B.-W., Wang, C.-Y., & Zhang, H.
Affiliations
  • Tongji Hospital (CN)
  • Guilin Medical University (CN)
  • Central South University (CN)
  • ShanghaiTech University (CN)
Corresponding author
  • Wang, Yi
  • Wang, Cong-Yi
  • Zhang, Huilan
Venue
Cell Death & Differentiation
Published
2020-11-03
Volume
28
Issue
4
Pages
1270-1283
ISSN
  • 1350-9047 (ISSN-L)
  • 1476-5403
OpenAlex
W3095707317
Cited by
153
References
48
Citations by year
2026: 24 · 2025: 37 · 2024: 39 · 2023: 21 · 2022: 22 · 2021: 9
FWCI
7.61
Type
journal article
Language
en
Open access
Locations
  • Cell Death and Differentiation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81530024)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
IL-24, idiopathic pulmonary fibrosis, bleomycin-induced lung fibrosis, M2 macrophages, IL-4, SOCS1, SOCS3, TGF-β1, macrophage polarization, pulmonary fibrosis
MeSH terms
Interleukin-24, Animals, Bleomycin, Disease Models, Animal, Female, Humans, Interleukins, Macrophages, Male, Mice, Inbred C57BL, Pulmonary Fibrosis, Signal Transduction, Interleukin-4, Mice, Knockout, Mice, Transforming Growth Factor beta1

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