Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver

摘要: Regulatory T cells (T(regs)) are found at sites of chronic inflammation where they mediate bystander and Ag-specific suppression local immune responses. However, little is known about the molecular control T(reg) recruitment into inflamed human tissues. We report that up to 18% in areas liver disease forkhead family transcriptional regulator box P3 (FoxP3)(+) T(regs). isolated CD4(+)CD25(+)CD127(low)FoxP3(+) T(regs) from chronically removed transplantation; compared with blood-derived T(regs), liver-derived express high levels chemokine receptors CXCR3 CCR4. In flow-based adhesion assays using hepatic sinusoidal endothelium, used alpha4beta1 bind transmigrate, whereas CCR4 played no role. The ligands CCL17 CCL22 were absent healthy liver, but detected their expression was restricted dendritic (DCs) within inflammatory infiltrates. These DCs closely associated CD8 CCR4(+) parenchyma septal areas. Ex vivo, migrated secreted by intrahepatic DCs. propose mediates via endothelium recruit patients hepatitis. Thus, different play distinct roles positioning hepatitis disease.