Bibliographic Details
| Title: |
Anti-PD-1 exacerbates bleomycin-induced lung injury in mice via Caspase-3/GSDME-mediated pyroptosis |
| Authors: |
Fei Wang, Haiyi Deng, Maolin Zhou, Yilin Yang, Jiankui Zhou, Yansheng Wang, Xiaohong Xie, Xinqing Lin, Ming Liu, Gengyun Sun, Chengzhi Zhou |
| Source: |
Cell Death and Disease, Vol 16, Iss 1, Pp 1-12 (2025) |
| Publisher Information: |
Nature Publishing Group, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
Cytology, QH573-671 |
| More Details: |
Abstract Immune checkpoint inhibitors (ICIs) have significant therapeutic effects but can also cause fatal lung injury. However, the lack of mouse animal models of ICI-related lung injury (ICI-LI) has limited the in-depth exploration of its pathogenesis. In clinical practice, underlying lung diseases increase the risk of lung injury. Thus, we used a mouse model of lung injury induced by bleomycin (BLM) and then administered anti-programmed cell death 1 (aPD-1) antibodies to induce ICI-LI. Compared with the BLM group, the aPD-1 + BLM group presented more significant weight loss, greater levels of lung inflammation and fibrosis, and decreased lung function. In this ICI-LI model, high levels of caspase-3/gasdermin E (GSDME) were detected in the lung tissue of mice, and the JNK inhibitor SP600125 mitigated lung damage by inhibiting GSDME-mediated pyroptosis. Consistent with the findings in the animal model, immunofluorescence and RNA sequencing of lung tissue from ICI-LI patients revealed upregulation of the expression of genes related to the GSDME-related pyroptosis pathway. Our results suggest that GSDME-mediated pyroptosis may be associated with the pathogenesis of ICI-LI, indicating that targeting GSDME could be a potential therapeutic strategy for treating ICI-LI. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-024-07319-9 |
| Access URL: |
https://doaj.org/article/56f98409dbc141a9a8ecfd132698c377 |
| Accession Number: |
edsdoj.56f98409dbc141a9a8ecfd132698c377 |
| Database: |
Directory of Open Access Journals |
