Impaired interferon-γ signaling promotes the development of silicosis

Zhouyangfan Peng, Mingwu Duan, Yiting Tang, Jianfeng Wu, Kai Zhao, Yanjun Zhong, Zhihui He, Jie Meng, Fangping Chen, Xianzhong Xiao, Haichao Wang, Timothy R. Billiar, Ben Lu*, Fang Liang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Silicosis is caused by inhalation of crystalline silica dust particles and known as one of the most serious occupational diseases worldwide. However, little is known about intrinsic factors leading to disease susceptibility. Single-cell sequencing of bronchoalveolar lavage fluid cells of mine workers with silicosis and their co-workers who did not develop silicosis revealed that the impaired interferon (IFN)-γ signaling in myeloid cells was strongly associated with the occurrence of silicosis. Global or myeloid cell-specific deletion of interferon γ receptor (IFN-γR) markedly enhanced the crystalline silica-induced pulmonary injury in wild-type but not in NLRP3 deficient mice. In vitro, IFN-γ priming of macrophages suppressed the crystalline silica-induced NLRP3 inflammasome activation partly by inducing the formation of spacious phagosomes with relatively reduced ratio of crystalline silica/phagosomal areas volumes to resistant crystalline silica-induced lysosomal membrane damage. Thus, these findings provide molecular insights into the intricate mechanisms underlying innate immunity-mediated host responses to environmental irritants.

Original languageEnglish
Article number104647
Issue number7
StatePublished - 15 Jul 2022
Externally publishedYes


  • Molecular biology
  • Molecular physiology
  • Physiology


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