Lymphatic Precollectors Contain a Novel, Specialized Subpopulation of Podoplanin super(low), CCL27-Expressing Lymphatic Endothelial Cells

Expression of the lymphoendothelial marker membrane mucoprotein podoplanin (podo) distinguishes endothelial cells of both blood and lymphatic lineages. We have previously discovered two distinct subpopulations of lymphatic endothelial cells (LECs) in human skin that were defined by their cell surface densities of podoplanin and were designated LEC super(podo-low) and LEC super(podo-high). LEC super(podo-high) is restricted to lymphatic precollector vessels that originate from initial LEC super(podo-high)-containing lymphatic capillaries and selectively express several pro-inflammatory factors. In addition to the chemokine receptor protein Duffy blood group antigen receptor for chemokines, these factors include the constitutively expressed chemokine CCL27, which is responsible for the accumulation of pathogenic CCR10 super(+) T lymphocytes in human inflammatory skin diseases. In this study, we report that CCR10 super(+) T cells accumulate preferentially both around and within CCL27 super(+) LEC super(podo-low) precollector vessels in skin biopsies of human inflammatory disease. In transmigration assays, isolated CCR10 super(+) T lymphocytes are chemotactically attracted by LEC super(podo-low) in a CCL27-dependent fashion, but not by LEC super(podo-high). These observations indicate that LEC super(podo-low)-containing precollector vessels constitute a specialized segment of the initial lymphatic microvasculature, and we hypothesize that these LEC super(podo-high)-containing vessels are involved in the trafficking of CCR10 super(+) T cells during skin inflammation.