@article{8129539f0e1545538b51857e518612a0,
title = "TRIB2 safeguards naive T cell homeostasis during aging",
abstract = "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.",
keywords = "CP: Immunology, T cell aging, T cell homeostasis, TRIB2, immunosenescence, naive T cells, virtual memory T cell",
author = "Wenqiang Cao and Ines Sturmlechner and Huimin Zhang and Jun Jin and Bin Hu and Jadhav, {Rohit R.} and Fengqin Fang and Weyand, {Cornelia M.} and Goronzy, {J{\"o}rg J.}",
note = "Funding Information: We thank R. Bosselut and P.E. Love from the National Institutes of Health for providing mouse strains and Xin Yang (Stanford University) for assistance in mouse studies. This work was supported by National Institutes of Health (NIH) R01AR042527, R01HL117913, R01AI108906, and R01HL142068 (all to C.M.W.); NIH R01AI108891, R01AG045779, R01AI129191, and U19AI057266 (all to J.J.G.); NIH T32AG049672 (to I.S.); and the National Natural Science Foundation of China 32270938 (to W.C.). This study was supported with resources and the use of facilities at the Palo Alto Veterans Administration Healthcare System and the Mayo Clinic Microscope and Cell Analysis Core. I.S. is a Glenn Foundation for Medical Research Postdoctoral Fellow. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. W.C. C.M.W. and J.J.G. designed the study. W.C. I.S. H.Z. J.J. and F.F. performed experiments. B.H. and R.R.J. analyzed transcriptomic and ATAC-seq data. W.C. I.S. C.M.W. and J.J.G. analyzed and interpreted data. W.C. I.S. and J.J.G. wrote the manuscript with input from all authors. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: We thank R. Bosselut and P.E. Love from the National Institutes of Health for providing mouse strains and Xin Yang (Stanford University) for assistance in mouse studies. This work was supported by National Institutes of Health (NIH) R01AR042527 , R01HL117913 , R01AI108906 , and R01HL142068 (all to C.M.W.); NIH R01AI108891 , R01AG045779 , R01AI129191 , and U19AI057266 (all to J.J.G.); NIH T32AG049672 (to I.S.); and the National Natural Science Foundation of China 32270938 (to W.C.). This study was supported with resources and the use of facilities at the Palo Alto Veterans Administration Healthcare System and the Mayo Clinic Microscope and Cell Analysis Core. I.S. is a Glenn Foundation for Medical Research Postdoctoral Fellow. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = mar,
day = "28",
doi = "10.1016/j.celrep.2023.112195",
language = "English (US)",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}