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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05 January 2021
A Correction to this paper has been published: https://doi.org/10.1038/s41418-020-00721-8
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (81530024, 91749207, 81920108009, 81770823, 81760008, 81800068, and 81670929), the Ministry of Science and Technology (2016YFC1305002 and 2017YFC1309603), NHC Drug Discovery Program (2017ZX09304022-07), the Department of Science and Technology of Hubei State (2017ACA096), the Guangxi Natural Science Foundation Program (2018GXNSFDA281041), the Integrated Innovative Team for Major Human Disease Programs of Tongji Medical College, Huazhong University of Science and Technology, and the Innovative Funding for Translational Research from Tongji Hospital.
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The original online version of this article was revised: In the “Acknowledgments” part, the funding number “9174927” (in the second line) should be corrected to “91749207”.
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Rao, LZ., Wang, Y., Zhang, L. et al. IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages. Cell Death Differ 28, 1270–1283 (2021). https://doi.org/10.1038/s41418-020-00650-6
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DOI: https://doi.org/10.1038/s41418-020-00650-6
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