1. Interleukin-17A plays a key role in pulmonary fibrosis following Propionibacterium acnes -induced sarcoidosis-like inflammation.
- Author
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Jiang D, Xiao H, Zheng X, Dong R, Zhang H, and Dai H
- Subjects
- Animals, Humans, Mice, Granuloma pathology, Inflammation, Interleukin-17 metabolism, Mice, Inbred C57BL, Propionibacterium acnes metabolism, Pulmonary Fibrosis, Sarcoidosis
- Abstract
Sarcoidosis is a granulomatous disease of unknown etiology, with limited therapeutic options. Chronic sarcoidosis can result in pulmonary fibrosis and can be lethal. Enhanced expression of pro-inflammatory cytokines, such as interleukin-17A (IL-17A), has been observed in sarcoid granulomas in humans. However, the role of IL-17A in the pathogenesis of chronic sarcoidosis or sarcoidosis-related pulmonary fibrosis and its potential therapeutic effects remain unclear. This study investigated whether IL-17A is critical in granulomatosis and its role in chronic inflammation in a profibrotic manner. Wild-type and IL-17A-knockout C57BL/6 mice were repeatedly challenged with heat-killed Propionibacterium acnes (PA) to induce sarcoidosis-like granulomata and sarcoidosis-related pulmonary fibrosis. Wild-type mice with granulomatosis were treated with anti-IL-17A antibody. Administration of PA enhanced the expression of IL-17A, granulomatosis, and fibrosis in mouse lungs after boost stimulation. Neither granulomata nor fibrosis were observed in IL-17A-knockout mice, even in the presence of interferon-γ enhancement. Neutralizing IL-17A antibody reduced inflammatory cells in bronchoalveolar lavage fluid and ameliorated both granulomatosis and fibrosis in sarcoidosis mice. In conclusion, our data demonstrate that IL-17A plays a critical role in PA-induced sarcoidosis-like inflammation in both granulomatosis inflammation and disease progression to pulmonary fibrosis, thus providing novel insights into the treatment of chronic sarcoidosis or sarcoidosis-related pulmonary fibrosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2023
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