Themis controls T cell activation, effector functions, and metabolism of peripheral CD8 + T cells.

Autor:	Gautam N; Translational Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Wojciech L; Translational Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Yap J; Translational Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Chua YL; Translational Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Ding EM; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Sim DC; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Tan AS; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Ahl PJ; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Prasad M; Translational Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Tung DW; Translational Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Connolly JE; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Adriani G; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore., Brzostek J; Translational Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Gascoigne NR; Translational Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore micnrjg@nus.edu.sg.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Translational Cancer Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2023 Sep 22; Vol. 6 (12). Date of Electronic Publication: 2023 Sep 22 (Print Publication: 2023).
DOI:	10.26508/lsa.202302156
Abstrakt:	Themis is important in regulating positive selection of thymocytes during T cell development, but its role in peripheral T cells is less understood. Here, we investigated T cell activation and its sequelae using a tamoxifen-mediated, acute Themis deletion mouse model. We find that proliferation, effector functions including anti-tumor killing, and up-regulation of energy metabolism are severely compromised. This study reveals the phenomenon of peripheral adaptation to loss of Themis, by demonstrating direct TCR-induced defects after acute deletion of Themis that were not evident in peripheral T cells chronically deprived of Themis in dLck-Cre deletion model. Peripheral adaptation to long-term loss was compared using chronic versus acute tamoxifen-mediated deletion and with the (chronic) dLck-Cre deletion model. We found that upon chronic tamoxifen-mediated Themis deletion, there was modulation in the gene expression profile for both TCR and cytokine signaling pathways. This profile overlapped with (chronic) dLck-Cre deletion model. Hence, we found that peripheral adaptation induced changes to both TCR and cytokine signaling modules. Our data highlight the importance of Themis in the activation of CD8 + T cells. (© 2023 Gautam et al.)
Databáze:	MEDLINE
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