BHLHE40 Orchestrates Effector Tissue-Resident Memory CD8⁺ T Cells and Limits Long-Term Survival of Kidney Graft.

ABSTRACT: Tissue-resident memory T cells (T_RM), which function against tumors, infections, and non-self antigens in organ transplantation, exhibit both effector and memory functionality. However, the homeostasis and differentiation of T_RM is not clear. Using a murine kidney transplant model for long-term observation, our single-cell and spatial transcriptomics showed that CD49a⁺PD1^hi CD8⁺ T_RM exhibited an effector phenotype with enhanced cytotoxicity at a later stage. This subset might mature from a CXCR6^hi precursor-like state with proliferation capacity in tertiary lymphoid structures (TLSs) in allografts. Mechanically, BHLHE40 is required for CD49a⁺PD1^hi CD8⁺ T_RM differentiatio

SUBMITTER: Li J 

PROVIDER: S-EPMC12915110 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature