1. TRIB2 safeguards naive T cell homeostasis during aging
- Author
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Wenqiang Cao, Ines Sturmlechner, Huimin Zhang, Jun Jin, Bin Hu, Rohit R. Jadhav, Fengqin Fang, Cornelia M. Weyand, and Jörg J. Goronzy
- Subjects
CP: Immunology ,Biology (General) ,QH301-705.5 - Abstract
Summary: 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.
- Published
- 2023
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