Distinct control of T cell proliferation and effector function by partitioning of intracellular sulfur from cysteine.

ABSTRACT: Delineating how acquired nutrients are partitioned into different intracellular pathways, and how these various fates support distinct functions in T cells is limited. We show that CD8⁺ T cells acquire cysteine to serve both as a substrate for glutathione (GSH) production, which modulates effector functions, and to cede its sulfur for NFS1-dependent FeS-cluster synthesis, which supports proliferation. NFS1 deletion in activated CD8⁺ T cells promotes exhaustion and dampens anti-cancer immunity, while blocking cysteine flux into GSH, or enforcing FeS metabolism, enhance tumor control. This role for disrupted FeS metabolism in T cell exhaustion is echoed in data from human HCC. Elucidating how different intracellular pathways use cysteine enables targeted control of cyst

SUBMITTER: Kelly B 

PROVIDER: S-EPMC12873821 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature