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TRIM22 negatively regulates MHC-II expression
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| Title: | TRIM22 negatively regulates MHC-II expression |
| Authors: | Inoue, Ayano Browse this author | | Watanabe, Masashi Browse this author →KAKEN DB | | Kondo, Takeshi Browse this author | | Hirano, Satoshi Browse this author →KAKEN DB | | Hatakeyama, Shigetsugu Browse this author →KAKEN DB |
| Keywords: | TRIM22 | | MHC-II | | Ubiquitin | | Checkpoint blockade immunotherapy | | IFN-γ |
| Issue Date: | Oct-2022 |
| Publisher: | Elsevier |
| Journal Title: | Biochimica et Biophysica Acta (BBA) Molecular Cell Research |
| Volume: | 1869 |
| Issue: | 10 |
| Start Page: | 119318 |
| Publisher DOI: | 10.1016/j.bbamcr.2022.119318 |
| Abstract: | The development of cancer treatment has recently achieved a remarkable breakthrough, and checkpoint blockade immunotherapy has received much attention. To enhance the therapeutic efficacy of checkpoint blockade immunotherapy, recent studies have revealed the importance of activation of CD4+ T cells via an in-crease in major histocompatibility complex (MHC) class II molecules in cancer cells. Here, we demonstrate that tripartite motif-containing (TRIM) 22, negatively regulates MHC-II expression. Gene knockout of TRIM22 using Cas9-sgRNAs led to an increase of MHC-II proteins, while TRIM22 overexpression remarkably decreased MHC-II proteins. mRNA levels of MHC-II and class II transactivator (CIITA), which plays an essential role in the regu-lation of MHC-II transcription, were not affected by TRIM22. Furthermore, TRIM22 knockout did not suppress the degradation of MHC-II protein but rather promoted it. These results suggest that TRIM22 decreases MHC-II protein levels through a combination of multiple mechanisms other than transcription or degradation. We showed that inhibition of TRIM22 can increase the amount of MHC-II expression in cancer cells, suggesting a possibility of providing the biological basis for a possible therapeutic target to potentiate checkpoint blockade immunotherapy. |
| Rights: | © 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/90585 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 畠山 鎮次
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