TRIB2 safeguards naive T cell homeostasis during aging.

Wenqiang Cao, Ines Sturmlechner, Huimin Zhang, Jun Jin, Bin Hu, Rohit R Jadhav, Fengqin Fang, Cornelia M Weyand, Jörg J Goronzy

Cell reports 2023 Mar 28

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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. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Wenqiang Cao, Ines Sturmlechner, Huimin Zhang, Jun Jin, Bin Hu, Rohit R Jadhav, Fengqin Fang, Cornelia M Weyand, Jörg J Goronzy. TRIB2 safeguards naive T cell homeostasis during aging. Cell reports. 2023 Mar 28;42(3):112195