β-Catenin in Dendritic Cells Negatively Regulates CD8 T Cell Immune Responses through the Immune Checkpoint Molecule Tim-3.

ABSTRACT: Recent studies have demonstrated that β-catenin in dendritic cells (DCs) serves as a key mediator in promoting both CD4 and CD8 T cell tolerance, although the mechanisms underlying how β-catenin exerts its functions remain incompletely understood. Here, we report that activation of β-catenin leads to the up-regulation of inhibitory molecule T-cell immunoglobulin and mucin domain 3 (Tim-3) in type 1 conventional DCs (cDC1s). Using a cDC1-targeted vaccine model with anti-DEC-205 engineered to express the melanoma antigen human gp100 (anti-DEC-205-hgp100), we demonstrated that CD11c-β-catenin^active mice exhibited impaired cross-priming and memory responses of gp100-specific CD8 T (Pmel-1) cells upon immunization with anti-DEC-205-hgp100. Single-cell RNA sequencing (scRNA-seq) analy

SUBMITTER: Fu C 

PROVIDER: S-EPMC11125945 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature