Abstract
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.
MeSH terms
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Aging / immunology
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Animals
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Autoimmune Diseases / immunology*
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Autoimmune Diseases / pathology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / pathology
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Chemokine CCL21
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Chemokines, CC / metabolism*
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Diabetes Mellitus / immunology*
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Diabetes Mellitus / pathology
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Disease Models, Animal
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Epithelial Cells / immunology
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Glycoproteins / metabolism*
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Immunohistochemistry
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Islets of Langerhans / immunology
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Islets of Langerhans / metabolism
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Islets of Langerhans / pathology
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Keratins / metabolism
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Lymphatic Vessels / immunology*
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Lymphatic Vessels / metabolism
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Lymphatic Vessels / pathology
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Lymphocyte Activation / immunology
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Membrane Glycoproteins / metabolism
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Membrane Transport Proteins
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Mice
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Mice, Inbred NOD
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Platelet Endothelial Cell Adhesion Molecule-1 / immunology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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Thymus Gland / immunology*
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Thymus Gland / metabolism
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Thymus Gland / pathology
Substances
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Ccl21a protein, mouse
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Chemokine CCL21
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Chemokines, CC
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Glycoproteins
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Gp38 protein, mouse
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Membrane Glycoproteins
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Membrane Transport Proteins
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Platelet Endothelial Cell Adhesion Molecule-1
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Xlkd1 protein, mouse
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Keratins