doi: 10.1002/ctm2.509

Protective function of interleukin‐22 in pulmonary fibrosis

Jun Yang+4 authors

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^{Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing Jiangsu, China,}

^{Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing Jiangsu, China,}

^{Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing Jiangsu, China,}

^{Wuxi Transplant Center, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi Jiangsu, China,}

^{Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing China,}

^{Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing Jiangsu, China,}

^{Department of Pharmacology and Toxicology, School of Pharmacy; University of Arizona, Tucson AZ,}

^{Asthma & Airway Disease Research Center, University of Arizona, Tucson AZ,}

Yonglong Xiao, Email: moc.361@36gnolyx.

Contributor Information.

^{Corresponding author.}

^{Correspondence}
Yonglong Xiao, MD, Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China.
Email: moc.361@36gnolyx,
Yin Chen, PhD, Department of Pharmacology and Toxicology, 1703 E Mabel Street RM232, Tucson, Arizona, USA.
Email: ude.anozira.ycamrahp@nehcy,
Mengshu Cao, MD, PhD, Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China.
Email: moc.621@oacuhsgnem,

^{These authors contributed equally to this work.}

Received 2020 Aug 28; Revised 2021 Jul 11; Accepted 2021 Jul 14.

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive scarring disease with unknown etiology. The evidence of a pathogenic role for transforming growth factor‐beta (TGF‐β) in the development and progression of IPF is overwhelming. In the present study, we investigated the role of interleukin‐22 (IL‐22) in the pathogenesis of IPF by regulating the TGF‐β pathway. We measured parameters and tissue samples from a clinical cohort of IPF. IL‐22R knock out (IL‐22RA1^{) and IL‐22 supplementation mouse models were used to determine if IL‐22 is protective in vivo. For the mechanistic study, we tested A549, primary mouse type II alveolar epithelial cell, human embryonic lung fibroblast, and primary fibroblast for their responses to IL‐22 and/or TGF‐β1. In a clinical cohort, the expression level of IL‐22 in the peripheral blood and lung tissues of IPF patients was lower than healthy controls, and the lower IL‐22 expression was associated with poorer pulmonary function. IL‐22R}^{mice demonstrated exacerbated inflammation and fibrosis. Reciprocally, IL‐22 augmentation by intranasal instillation of recombinant IL‐22 repressed inflammation and fibrotic phenotype. In vitro, IL‐22 treatment repressed TGF‐β1 induced gene markers representing epithelial‐mesenchymal‐transition and fibroblast‐myofibroblast‐transition, likely via the inhibition of TGF‐β receptor expression and subsequent Smad2/3 activation. IL‐22 appears to be protective against pulmonary fibrosis by inhibiting TGF‐β1 signaling, and IL‐22 augmentation may be a promising approach to treat IPF.}

Keywords: fibrosis, IL‐22, IPF, TGF‐β

Abstract

Supporting Information

Click here for additional data file.^{(1.1M, pdf)}

Supporting Information

Click here for additional data file.^{(18K, docx)}

Supporting Information

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Notes

Gu P, Wang D, Zhang Ji, et al. Protective function of interleukin‐22 in pulmonary fibrosis. Clin Transl Med. 2021;11:e509. 10.1002/ctm2.509 [CrossRef] [Google Scholar]

Notes

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