한빛사논문
- 조회1,116
Jihyun Park1, Si-Yeon Lee2, Yoon Jeon3, Kyung-Mo Kim2, Jin-Kwan Lee4, Jiwon Ko5, Eun-Ji Park2, Joon-Sup Yoon2, Baeki E Kang2, Dongryeol Ryu6, Ho Lee3, Su-Jin Shin7, Heounjeong Go8, and Chang-Woo Lee2,*
1Dept. of Health Sciences and Technology, Sungkyunkwan University
2Dept. of Molecular Cell Biology, Sungkyunkwan University of School of Medicine
3Research Institute, National Cancer Center
4Research Institute, Curogen Technology
5University of Ulsan College of Medicine, Asan Medical Center
6Dept. of Molecular Cell Biology, Sungkyunkwan University School of Medicine
7Pathology, Hanyang University
8Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine
*Corresponding Author.
Abstract
CD8+ T cells play an important role in the elimination of tumors. However, the underlying mechanisms involved in eliciting and maintaining effector responses in CD8+ T cells remain to be elucidated. Pellino1 (Peli1) is a receptor signal-responsive ubiquitin E3 ligase, which acts as a critical mediator for innate immunity. Here, we found that the risk of developing tumors was dependent on Peli1 expression. Peli1 was upregulated in CD8+ T cells among tumor-infiltrating lymphocytes (TIL). In contrast, a deficit of Peli1 enhanced the maintenance and effector function of CD8+ TILs. The development of Peli1-deficient CD8+ TILs prevented T-cell exhaustion and retained the hyperactivated states of T cells to eliminate tumors. We also found that Peli1 directly interacted with protein kinase C-theta (PKCθ), a central kinase in T-cell receptor downstream signal transduction, but whose role in tumor immunology remains unknown. Peli1 inhibited the PKCθ pathway by lysine 48–mediated ubiquitination degradation in CD8+ TILs. In summary, the Peli1–PKCθ signaling axis is a common inhibitory mechanism that prevents antitumor CD8+ T-cell function, and thus targeting Peli1 may be a useful therapeutic strategy for improving cytotoxic T-cell activity.
논문정보
- Research article
- 2022년 01월 (BRIC 등록일 2022-02-15)
- 국내 연구진
- 생명과학 > 유전자발현
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