| First Author | Gautam N | Year | 2023 |
| Journal | Life Sci Alliance | Volume | 6 |
| Issue | 12 | PubMed ID | 37739454 |
| Mgi Jnum | J:341193 | Mgi Id | MGI:7532131 |
| Doi | 10.26508/lsa.202302156 | Citation | Gautam N, et al. (2023) Themis controls T cell activation, effector functions, and metabolism of peripheral CD8(+) T cells. Life Sci Alliance 6(12) |
| abstractText | 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. |
