TRIM22 negatively regulates MHC-II expression

Inoue, Ayano; Watanabe, Masashi; Kondo, Takeshi; Hirano, Satoshi; Hatakeyama, Shigetsugu

TRIM22 negatively regulates MHC-II expression

Inoue, Ayano; Watanabe, Masashi; Kondo, Takeshi et al.

Biochimica et Biophysica Acta (BBA) Molecular Cell Research, 2022, 1869(10), 119318

Permalink : https://hdl.handle.net/2115/90585

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アクセス権	open access
URI	https://hdl.handle.net/2115/90585
タイトル	TRIM22 negatively regulates MHC-II expression
著者	Inoue, Ayano ; Watanabe, Masashi ; Kondo, Takeshi ; Hirano, Satoshi ; Hatakeyama, Shigetsugu
著者名 Inoue, Ayano
e-Rad_Researcher 10632424 著者名 Watanabe, Masashi
著者名 Kondo, Takeshi
e-Rad_Researcher 50322813 著者名 Hirano, Satoshi
e-Rad_Researcher 70294973 著者名 Hatakeyama, Shigetsugu
言語	英語
キーワード	TRIM22
	MHC-II
	Ubiquitin
	Checkpoint blockade immunotherapy
	IFN-γ
発行日	2022-10
出版者	Elsevier
収録物名	Biochimica et Biophysica Acta (BBA) Molecular Cell Research
巻(号)	1869(10)
ページ	119318
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 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/
PISSN	0167-4889
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.bbamcr.2022.119318