TY - JOUR
T1 - PREX1 improves homeostatic proliferation to maintain a naive CD4+ T cell compartment in older age
AU - Zhang, Huimin
AU - Okuyama, Hirohisa
AU - Jain, Abhinav
AU - Jadhav, Rohit R.
AU - Wu, Bowen
AU - Sturmlechner, Ines
AU - Morales, Jose
AU - Ohtsuki, Shozo
AU - Weyand, Cornelia M.
AU - Goronzy, Jӧrg J.
N1 - Publisher Copyright:
© 2024, Zhang et al.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85187125750&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.172848
DO - 10.1172/jci.insight.172848
M3 - Article
C2 - 38329813
AN - SCOPUS:85187125750
SN - 2379-3708
VL - 9
JO - JCI Insight
JF - JCI Insight
IS - 5
M1 - e172848
ER -