Heme and iron toxicity in the aged spleen impairs T cell immunity through iron deprivation.

ABSTRACT: Mechanisms of T cell aging involve cell-intrinsic alterations and interactions with immune and stromal cells. Here we found that splenic T cells exhibit greater functional decline than lymph node T cells within the same aged mouse, prompting investigation into how the aged spleen contributes to T cell aging. Proteomic analysis revealed increased expression of heme detoxification in aged spleen-derived lymphocytes. Exposure to the heme- and iron-rich aged splenic microenvironment induced aging phenotypes in young T cells, including reduced proliferation and CD39 upregulation. T cells survived this hostile niche by maintaining a low labile iron pool, at least in part, via IRP2 downregulation to resist ferroptosis but failed to induce sufficient iron uptake for activation. Iron supplementatio

SUBMITTER: Ezuz D 

PROVIDER: S-EPMC12618244 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature