Differential expression of CCL19 by DC-Lamp+ mature dendritic cells in human lymph node versus chronically inflamed...

De novo formation of lymphoid tissue is one of the characteristic features of chronic inflammation. The formation of T cell-mature dendritic cell (DC) clusters has been previously demonstrated in chronically inflamed skin infected with Candida albicans. A functional similarity was also found between chronic inflammation and the T-cell zone of lymph nodes (LNs), since a substantial fraction of phenotypically mature DCs in both tissues expressed CCL22 (macrophage-derived chemokine; MDC) and were closely surrounded by memory-type T cells expressing its receptor, CCR4. To analyse the nature of T cell-mature DC interactions further in chronically inflamed skin and LNs, the present study focuses on another chemokine system, namely CCL19 (EBI1 ligand chemokine; ELC), CCL21 (secondary lymphoid tissue chemokine; SLC) and their shared receptor, CCR7. RT-PCR analysis revealed expression of CCL19, CCL21, and CCR7 at high levels in LNs and at low levels in inflamed skin. Using immunohistochemistry, the majority of DC-Lamp(+) mature DCs in the T-cell area of LNs expressed CCL19 and were surrounded by CCR7(+) naïve-type lymphocytes, while CCL21 was expressed in reticular stromal cells and vascular endothelial cells. Very few mature DCs in LNs were found to express CCR7. In contrast, the majority of DC-Lamp(+) mature DCs in inflamed skin were totally negative for CCL19 and were surrounded by CCR7(-) memory-type T cells. Furthermore, CCL21 expression in the inflamed skin was detected in dermal lymphatic endothelial cells and rare CCR7(+) mature DCs were mostly seen within the lymphatic vessels. In normal skin, on the other hand, no cells immunoreactive for CCL19, CCL21, or CCR7 were found. The present study thus reveals a striking difference in the function of mature DCs between LNs and chronically inflamed skin.