Abstract
Objective:
Sjögren's syndrome is a chronic autoimmune disorder characterized by progressive lymphocytic infiltration within the salivary and lacrimal glands. This study was undertaken to investigate the effects of innate immunity activation on sialoadenitis in a mouse strain genetically susceptible for development of SS-like disease.
Methods:
Female New Zealand Black X New Zealand White F1 mice were repeatedly treated with toll-like 3 receptor agonist poly(I:C). Submandibular glands were investigated at different time points for sialoadenitis by immunohistochemistry and for gene expression of different chemokines by quantitative PCR. Submandibular gland-infiltrating cells were characterized by flow cytometry.
Results:
Poly(I:C) treatment significantly upregulated the expression of multiple chemokines within the submandibular glands. The severity and incidence of sialoadenitis was considerably higher in poly(I:C)-treated mice. There was a preponderance of dendritic cells and NK cells in the initial inflammatory cell infiltrates, and these were followed by CD4+ T cells.
Conclusions:
Our data clearly demonstrate that systemic activation of innate immunity accelerates sialoadenitis in a mouse model for SS-like disease. These findings suggest that chronic activation of innate immunity can influence certain features of SS.
© 2011 John Wiley & Sons A/S.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / pathology
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Chemokine CCL11 / analysis
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Chemokine CCL11 / drug effects
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Chemokine CCL2 / analysis
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Chemokine CCL2 / drug effects
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Chemokine CCL3 / analysis
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Chemokine CCL3 / drug effects
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Chemokine CCL4 / analysis
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Chemokine CCL4 / drug effects
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Chemokine CCL7 / analysis
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Chemokine CCL7 / drug effects
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Chemokine CXCL10 / analysis
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Chemokine CXCL10 / drug effects
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Chemokine CXCL13 / analysis
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Chemokine CXCL13 / drug effects
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Chemokines, CC / analysis
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Chemokines, CC / drug effects
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Chemokines, CXC / analysis
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Chemokines, CXC / drug effects
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Dendritic Cells / drug effects
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Dendritic Cells / pathology
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Disease Models, Animal
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Female
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Flow Cytometry
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Immunity, Innate / drug effects
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Immunity, Innate / immunology*
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / pathology
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Mice
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Mice, Inbred NZB
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Monocyte Chemoattractant Proteins / analysis
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Monocyte Chemoattractant Proteins / drug effects
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Poly I-C / pharmacology
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Real-Time Polymerase Chain Reaction
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Sialadenitis / immunology*
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Sialadenitis / pathology
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Sjogren's Syndrome / immunology*
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Sjogren's Syndrome / pathology
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Submandibular Gland Diseases / immunology
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Submandibular Gland Diseases / pathology
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Toll-Like Receptor 3 / agonists
Substances
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Ccl11 protein, mouse
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Ccl12 protein, mouse
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Ccl2 protein, mouse
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Ccl3 protein, mouse
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Ccl7 protein, mouse
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Chemokine CCL11
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Chemokine CCL2
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL7
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Chemokine CXCL10
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Chemokine CXCL13
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Chemokines, CC
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Chemokines, CXC
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Cxcl10 protein, mouse
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Cxcl13 protein, mouse
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Monocyte Chemoattractant Proteins
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TLR3 protein, mouse
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Toll-Like Receptor 3
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Poly I-C