@article{2b422321263448a18cf55f24ba0a97c2,
title = "Transcription factor networks in aged na{\"i}ve CD4 T cells bias lineage differentiation",
abstract = "With reduced thymic activity, the population of na{\"i}ve T cells in humans is maintained by homeostatic proliferation throughout adult life. In young adults, na{\"i}ve CD4 T cells have enormous proliferative potential and plasticity to differentiate into different lineages. Here, we explored whether na{\"i}ve CD4 T-cell aging is associated with a partial loss of this unbiased multipotency. We find that na{\"i}ve CD4 T cells from older individuals have developed a propensity to develop into TH9 cells. Two major mechanisms contribute to this predisposition. First, responsiveness to transforming growth factor β (TGFβ) stimulation is enhanced with age due to an upregulation of the TGFβR3 receptor that results in increased expression of the transcription factor PU.1. Secondly, aged na{\"i}ve CD4 T cells display altered transcription factor profiles in response to T-cell receptor stimulation, including enhanced expression of BATF and IRF4 and reduced expression of ID3 and BCL6. These transcription factors are involved in TH9 differentiation as well as IL9 transcription suggesting that the aging-associated changes in the transcription factor profile favor TH9 commitment.",
keywords = "T-cell lineage differentiation, aging, immunosenescence, interleukin 9, multipotency, transforming growth factor β",
author = "Bin Hu and Guangjin Li and Zhongde Ye and Gustafson, {Claire E.} and Lu Tian and Weyand, {Cornelia M.} and Goronzy, {J{\"o}rg J.}",
note = "Funding Information: This work was supported by the National Institutes of Health (R01 AI108891, R01 AG045779, U19 AI057266, R01 AI129191 to JJG and R01 AR042527, R01 HL117913, R01 AI108906 and P01 HL129941 to CMW). CEG was supported by the Diamond/AFAR Young Investigator Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Flow cytometry and/or fluorescence activated cell sort‐ ing was performed in the Palo Alto Veteran Administration Flow Cytometry Core supported by the US Department of Veterans Affairs and the Palo Alto Veterans Institute for Research. Technical assis‐ tance was provided by Dr. Corey Cain and Lusijah Rott. Sequencing was performed by the Stanford Functional Genomics Facility. Some of the computing for this project was performed using computational resources of the Stanford Research Computing Center. Funding Information: This work was supported by the National Institutes of Health (R01 AI108891, R01 AG045779, U19 AI057266, R01 AI129191 to JJG and R01 AR042527, R01 HL117913, R01 AI108906 and P01 HL129941 to CMW). CEG was supported by the Diamond/AFAR Young Investigator Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Flow cytometry and/or fluorescence activated cell sorting was performed in the Palo Alto Veteran Administration Flow Cytometry Core supported by the US Department of Veterans Affairs and the Palo Alto Veterans Institute for Research. Technical assistance was provided by Dr. Corey Cain and Lusijah Rott. Sequencing was performed by the Stanford Functional Genomics Facility. Some of the computing for this project was performed using computational resources of the Stanford Research Computing Center. Publisher Copyright: {\textcopyright} 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.",
year = "2019",
month = aug,
doi = "10.1111/acel.12957",
language = "English (US)",
volume = "18",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "4",
}