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• W4386956167 endingPage "e202302156" @default.
• W4386956167 startingPage "e202302156" @default.
• W4386956167 abstract "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." @default.
• W4386956167 created "2023-09-23" @default.
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• W4386956167 date "2023-09-22" @default.
• W4386956167 modified "2023-09-29" @default.
• W4386956167 title "Themis controls T cell activation, effector functions, and metabolism of peripheral CD8⁺T cells" @default.
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• W4386956167 doi "https://doi.org/10.26508/lsa.202302156" @default.
• W4386956167 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37739454" @default.
• W4386956167 hasPublicationYear "2023" @default.
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