AUTHOR=Peng Zhouyangfan , Duan Mingwu , Zhao Kai , Tang Yiting , Liang Fang 

TITLE=RAB20 deficiency promotes the development of silicosis via NLRP3 inflammasome

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.967299

DOI=10.3389/fimmu.2022.967299

ISSN=1664-3224

ABSTRACT=Silicosis is a worldwide serious occupational diseases that caused by inhalation of silica crystals. However, the pathogenesis mechanism of silicosis is little known. We performed single-cell sequencing in bronchoalveolar lavage fluid (BALF) from mine workers with silicosis and their co-workers who did not develop silicosis, and found that the RAB20 deficiency in monocytes/macrophages was strongly linked with the development of silicosis. In the silicosis murine model, RAB20 knockout markedly enhanced the silica crystals-induced pulmonary interstitial fibrosis and respiratory dysfunction. Besides, this process is strongly accompanied with IL-1β release and NLRP3 activation. In vitro, RAB20 knockout macrophages aggravated the crystalline silica-induced IL-1β release and NLRP3 inflammasome activation partly by increased ratio of crystalline silica/phagosomal areas/volumes to induce lysosomal injury. Thus, these findings provide novel molecular insights into the intricate mechanisms underlying lysosomal protein RAB20 is necessary for environmental irritants-mediated innate immunity, and shed light on the future development of novel therapy target for the prevention of silicosis.