Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation.

Abstract:

:With reduced thymic activity, the population of naïve T cells in humans is maintained by homeostatic proliferation throughout adult life. In young adults, naïve CD4 T cells have enormous proliferative potential and plasticity to differentiate into different lineages. Here, we explored whether naïve CD4 T-cell aging is associated with a partial loss of this unbiased multipotency. We find that naïve 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 naïve 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.

journal_name

Aging Cell

journal_title

Aging cell

authors

Hu B,Li G,Ye Z,Gustafson CE,Tian L,Weyand CM,Goronzy JJ

doi

10.1111/acel.12957

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

e12957

issue

4

eissn

1474-9718

issn

1474-9726

journal_volume

18

pub_type

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