Interleukin-17A plays a key role in pulmonary fibrosis following Propionibacterium acnes–induced sarcoidosis-like inflammation

• Published in: Experimental biology and medicine (Maywood, N.J.) Vol. 248; no. 14; pp. 1181 - 1190
• Main Authors: Jiang, Dingyuan, Xiao, Huijuan, Zheng, Xiaofen, Dong, Run, Zhang, Hongbing, Dai, Huaping
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.07.2023
• Subjects: Animals; Granuloma - pathology; Humans; Inflammation; Interleukin-17 - metabolism; Mice; Mice, Inbred C57BL; Original Research; Propionibacterium acnes - metabolism; Pulmonary Fibrosis; Sarcoidosis; sarcoidosis; IL-17A; granuloma; pulmonary fibrosis
• ISSN: 1535-3702; 1535-3699
• DOI: 10.1177/15353702231182224

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.