Aging-associated HELIOS deficiency in naive CD4⁺ T cells alters chromatin remodeling and promotes effector cell responses.

ABSTRACT: Immune aging combines cellular defects in adaptive immunity with the activation of pathways causing a low-inflammatory state. Here we examined the influence of age on the kinetic changes in the epigenomic and transcriptional landscape induced by T cell receptor (TCR) stimulation in naive CD4⁺ T cells. Despite attenuated TCR signaling in older adults, TCR activation accelerated remodeling of the epigenome and induced transcription factor networks favoring effector cell differentiation. We identified increased phosphorylation of STAT5, at least in part due to aberrant IL-2 receptor and lower HELIOS expression, as upstream regulators. Human HELIOS-deficient, naive CD4⁺ T cells, when transferred into human-synovium-mouse chimeras, infiltrated tissues more efficiently. Inh

SUBMITTER: Zhang H 

PROVIDER: S-EPMC10118794 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature