PREX1 Improves Homeostatic Proliferation To Maintain a Naive CD4+ T Cell Compartment in Older Age

Authors

Huimin Zhang
Hirohisa Okuyama
Abhinav Jain
Rohit R Jadhav
Bowen Wu
Ines Sturmlechner
Jose Morales
Shozo Ohtsuki
Cornelia M Weyand
Jӧrg J Goronzy

Publication Date

2-8-2024

Journal

JCI Insight

Abstract

The human adult immune system maintains normal T cell counts and compensates for T cell loss throughout life, mainly through peripheral homeostatic proliferation after the ability of the thymus to generate new T cells has rapidly declined at adolescence. This process is mainly driven by STAT5-activating cytokines, most importantly IL-7, and is very effective in maintaining a large naive CD4+ T cell compartment into older age. Here, we describe that naive CD4+ T cells undergo adaptations to optimize IL-7 responses by upregulating the guanine-nucleotide exchange factor PREX1 in older age. PREX1 promotes nuclear translocation of phosphorylated STAT5, thereby supporting homeostatic proliferation in response to IL-7. Through the same mechanism, increased expression of PREX1 also biases naive cells to differentiate into effector T cells. These findings are consistent with the concept that primarily beneficial adaptations during aging, i.e., improved homeostasis, account for unfavorable functions of the aged immune system, in this case biased differentiation.

Keywords

Adult, Humans, Aged, CD4-Positive T-Lymphocytes, STAT5 Transcription Factor, Interleukin-7, Cell Proliferation, Homeostasis, Guanine Nucleotide Exchange Factors

Comments

Supplementary Materials

PMID: 38329813