Lymphatic vascular endothelial hyaluronan receptor (LYVE)-1- and CCL21-positive lymphatic compartments in the diabetic thymus.
To explore the biological significance of the lymphatics in the autoimmune process, the thymus from non-obese diabetic (NOD) mice was evaluated by histochemistry and western blot analysis. Thymic lymphatic endothelial cells showed suggestive expression patterns of the functional molecules lymphatic vascular endothelial hyaluronan receptor (LYVE)-1, CCL21, CD31 and podoplanin. With increasing age, the expression of CCL21 was reduced in the medullary epithelial cells and lymphatics. Of note, LYVE-1-expressing lymphatics, filled with a cluster of thymocytes, increased in number and size and extended from the corticomedullary boundary into the medulla as the insulitis progressed. The development of lymphatic compartments was occasionally accompanied by a regional disappearance between the cortex and medulla. The CD4- and CD8-positive T cells frequently penetrated through the slender lymphatic walls. The epithelial reticular cell layer lining the perivascular spaces was extensively stained with cytokeratin, but the expression of cytokeratin showed an age-dependent decrease. These findings indicate that the occurrence of LYVE-1-expressing lymphatic compartments and the alteration of CCL21 expression in the lymphatics may be involved in defective thymocyte differentiation and migration, and play a significant role in insulitic and diabetic processes.
Ji
Rui-Cheng
RC
Department of Anatomy, Biology and Medicine, Oita University Faculty of Medicine, Oita, Japan. Ji@med.oita-u.ac.jp
Kurihara
Kazushige
K
Kato
Seiji
S
D000375:Aging / Q000276:immunology; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007633:Keratins / Q000378:metabolism; D042601:Lymphatic Vessels / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D016688:Mice, Inbred NOD; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000098853:Podoplanin
D054421:Chemokine CCL21; D019742:Chemokines, CC; D006023:Glycoproteins; D007633:Keratins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C515480:Ccl21a protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C492273:LYVE1 protein, mouse