Lymphatic precollectors contain a novel, specialized subpopulation of podoplanin 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 podo-low and LEC podo-high. LEC podo-low is restricted to lymphatic precollector vessels that originate from initial LEC 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+ T lymphocytes in human inflammatory skin diseases. In this study, we report that CCR10+ T cells accumulate preferentially both around and within CCL27+ LEC podo-low precollector vessels in skin biopsies of human inflammatory disease. In transmigration assays, isolated CCR10+ T lymphocytes are chemotactically attracted by LEC podo-low in a CCL27-dependent fashion, but not by LEC podo-high. These observations indicate that LEC podo-low-containing precollector vessels constitute a specialized segment of the initial lymphatic microvasculature, and we hypothesize that these LEC podo-low-containing vessels are involved in the trafficking of CCR10+ T cells during skin inflammation.
Wick
Nikolaus
N
Department of Pathology, Vienna Medical University, Vienna, Austria.
Haluza
Daniela
D
Gurnhofer
Elisabeth
E
Raab
Ingrid
I
Kasimir
Marie-Theres
MT
Prinz
Michael
M
Steiner
Carl-Walter
CW
Reinisch
Christina
C
Howorka
Anny
A
Giovanoli
Pietro
P
Buchsbaum
Sabine
S
Krieger
Sigurd
S
Tschachler
Erwin
E
Petzelbauer
Peter
P
Kerjaschki
Dontscho
D
D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D054425:Chemokine CCL27 / Q000378:metabolism*; D002633:Chemotaxis; D020405:Dermis / Q000098:blood supply / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007249:Inflammation / Q000235:genetics; D042601:Lymphatic Vessels / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D021381:Protein Transport; D054447:Receptors, CCR10 / Q000378:metabolism; D012871:Skin Diseases / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology; D000098853:Podoplanin
D054425:Chemokine CCL27; D008562:Membrane Glycoproteins; D054447:Receptors, CCR10; C492276:CCL27 protein, human; C515706:CCR10 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin
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