論文 - 詳細
| RRC ID | 85750 |
|---|---|
| 著者 | Zheng Y, Wang Z, Weng Y, Sitosari H, He Y, Zhang X, Shiotsu N, Fukuhara Y, Ikegame M, Okamura H. |
| タイトル | Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis. |
| ジャーナル | Sci Rep |
| Abstract |
Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) is believed to possess immune evasion capabilities, but it remains unclear whether this immune evasion is related to host gene alternative splicing (AS). In this study, RNA-sequencing revealed significant changes in both AS landscape and transcriptomic profile of macrophages following P. gingivalis infection with/without knockout of gingipain (a unique toxic protease of P. gingivalis). P. gingivalis infection increased the PD-L1 transcripts expression and selectively upregulated a specific coding isoform that more effectively binds to PD-1 on T cells, thereby inhibiting immune function. Biological experiments also detected AS switch of PD-L1 in P. gingivalis-infected or gingipain-treated macrophages. AlphaFold 3 predictions indicated that the protein docking compatibility between PD-1 and P. gingivalis-upregulated PD-L1 isoform was over 80% higher than another coding isoform. These findings suggest that P. gingivalis employs gingipain to modulate the AS of PD-L1, facilitating immune evasion. |
| 巻・号 | 15(1) |
| ページ | 10462 |
| 公開日 | 2025-3-26 |
| DOI | 10.1038/s41598-025-94954-7 |
| PII | 10.1038/s41598-025-94954-7 |
| PMID | 40140451 |
| PMC | PMC11947232 |
| MeSH | Alternative Splicing Animals B7-H1 Antigen* / chemistry B7-H1 Antigen* / genetics B7-H1 Antigen* / metabolism Bacteroidaceae Infections* / genetics Bacteroidaceae Infections* / immunology Bacteroidaceae Infections* / metabolism Bacteroidaceae Infections* / microbiology Gingipain Cysteine Endopeptidases* / genetics Gingipain Cysteine Endopeptidases* / metabolism Host-Pathogen Interactions Humans Immune Evasion Macrophages* / immunology Macrophages* / metabolism Macrophages* / microbiology Mice Porphyromonas gingivalis* / pathogenicity Protein Isoforms / genetics Protein Isoforms / metabolism |
| IF | 3.998 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |