CCR8-expressie op regulatoire T-cellen beschermt tegen myocardinfarctschade

BACKGROUND:Tissue-specific regulatory T cells (Tregs) accumulate in the heart after myocardial infarction (MI) and play a vital role in limiting inflammation and promoting tissue repair. However, the developmental trajectory of heart Tregs and the molecular cues that guide their recruitment to the heart remain poorly understood, impeding therapeutic strategies that leverage Treg-mediated cardiac protection.METHODS:We used single-cell and bulk RNA sequencing in a murine MI model to delineate the differentiation trajectory of Tregs from mediastinal lymph nodes to the heart. Functional validation was performed using Treg-specific CCR8 (CC motif chemokine receptor 8) knockout mice (Ccr8flox/floxFoxp3Cre), CCL1 (CC motif chemokine ligand 1) knockout mice (Ccl1−/−), macrophage-targeted CCL1 knockdown mice, CCL1-overexpressing mice, and DEREG mice. The CCL1-CCR8 axis was evaluated in cardiac tissues and circulating blood from patients with MI.RESULTS:Single-cell RNA sequencing revealed a step