Chemokine Receptor Expression on Normal Blood CD56⁺ NK-Cells Elucidates Cell Partners That Comigrate during the Innate and Adaptive Immune Responses and Identifies a Transitional NK-Cell Population

Figure 4

Diagram illustrating the complex relationship established between NK-cells and the other cells of the innate-dendritic cells (DC), monocytes, macrophages, neutrophils, and adaptive (T cells) immune system, whose homing to lymphoid organs and recruitment to inflamed tissues are mediated by the interaction of homeostatic chemokines constitutively expressed on locally resident cells and inflammatory chemokines, with the correspondent chemokine receptors. CCR7 expression on NK-cells, mature DC, and naïve T cells allows these cells to migrate into the lymph nodes, in response to CCL19 (ELC) and CCL21 (SLC) produced locally. CXCR3/CCR5 expression on NK-cells permits these cells to migrate into inflamed tissues, together with CCR5⁺ proinflammatory monocytes, CCR5/CXCR3⁺ Th1 cells, and CCR5/CXCR3⁺ cytotoxic T lymphocytes (CTL). CXCR1/CXCR2 expression on NK-cells, neutrophils, and CTL permits these cells to migrate into inflamed tissues in response to CXCL8 (IL-8), where they interact together and with activated macrophages. NK-cells are transitional NK-cells, whose properties are intermediate between those of and NK-cells. Dashed arrows indicate the routes of differentiation. Full arrows indicate the cross-talk between cells mediated by cytokines and chemokines. CCR7 ligands: CCL-19 (ELC) and CCL21 (SLC); CCR5 ligands: CCL3 (MIP-1), CCL4 (MIP-1), CCL5 (RANTES), and CCL8 (MCP-2); CXCR3 ligands: CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC); CXCL1 ligands: CXCL-8 (IL-8); CXCL2 ligands: CXCL-8 (IL-8) and other ELR motif containing CXCL chemokine; CXCR4 ligand: CXCL12 (SDF-1); CCR1 ligands: CCL3 (MIP-1), CCL5 (RANTES), MCP-2, and MCP-3; CCR2 ligands: CCL2 (MCP-1), CCL8 (MCP-2), CCL7 (MCP-3), and CCL13 (MCP-4).