Expression of Toll-like receptors 2 and 4 on human intestinal lymphatic vessels.

The Toll-like receptor (TLR) is a part of the innate immune system sensing pathogen-associated molecular patterns (PAMPs). Recently, TLRs 2 and 4 have been demonstrated for the ligand engagements, which result in the induction of cytokines. Here we investigated the expression of TLRs 2 and 4 on lymphatic vessels producing cys-cys chemokine ligand 21 (CCL21) in the human small intestine. The specificity of antibodies to TLRs was tested on a human monocyte leukemia cell line, umbilical vein endothelial cells (HUVEC), and periodontal ligament fibroblasts (PDLF) with the examination for the TLR gene expression by the reverse transcription-polymerase chain reaction (RT-PCR), and lymphatic vessels were identified by antibodies for platelet-endothelial cell adhesion molecule-1 (PECAM-1) and desmoplakin. The expression of CCL21 was not clearly detected on collecting lymphatic vessels in the submucosa while it was generally observed on the central lacteals of villi and lymphatic capillaries in the lamina propria mucosae. The reaction of antibodies to TLRs 2 and 4 was also not clearly detected on collecting lymphatic vessels in the submucosa and central lacteals of villi, but generally observed on lymphatic capillaries expressing CCL21 in the lamina propria mucosae of tissue where the expression of CCL21 and TLRs was not clearly observed in blood vessels. These may suggest that the expression of CCL21, and TLRs 2 and 4 is predominantly induced in the peripheral lymphatic endothelium of the small intestinal microcirculation. The lymphatic endothelium may contribute to allow dendritic cells to home into secondary lymphoid tissue through the expression of TLRs, the ligand engagements of which result in the induction of chemokines.