| First Author | Cao W | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 3 | Pages | 112195 |
| PubMed ID | 36884349 | Mgi Jnum | J:334931 |
| Mgi Id | MGI:7450658 | Doi | 10.1016/j.celrep.2023.112195 |
| Citation | Cao W, et al. (2023) TRIB2 safeguards naive T cell homeostasis during aging. Cell Rep 42(3):112195 |
| abstractText | Naive CD4(+) T cells are more resistant to age-related loss than naive CD8(+) T cells, suggesting mechanisms that preferentially protect naive CD4(+) T cells during aging. Here, we show that TRIB2 is more abundant in naive CD4(+) than CD8(+) T cells and counteracts quiescence exit by suppressing AKT activation. TRIB2 deficiency increases AKT activity and accelerates proliferation and differentiation in response to interleukin-7 (IL-7) in humans and during lymphopenia in mice. TRIB2 transcription is controlled by the lineage-determining transcription factors ThPOK and RUNX3. Ablation of Zbtb7b (encoding ThPOK) and Cbfb (obligatory RUNT cofactor) attenuates the difference in lymphopenia-induced proliferation between naive CD4(+) and CD8(+) cells. In older adults, ThPOK and TRIB2 expression wanes in naive CD4(+) T cells, causing loss of naivety. These findings assign TRIB2 a key role in regulating T cell homeostasis and provide a model to explain the lesser resilience of CD8(+) T cells to undergo changes with age. |
