title: Sjögren's syndrome-like ocular surface disease in thrombospondin-1 deficient mice.
abstract: Thrombospondin-1 (TSP-1) is a major activator of latent transforming growth factor-beta in vitro as well as in vivo. Mice deficient in TSP-1, despite appearing normal at birth, develop a chronic form of ocular surface disease that is marked by increased apoptosis and deterioration in the lacrimal gland, associated dysfunction, and development of inflammatory infiltrates that result in abnormal tears. The increase in CD4(+) T cells in the inflammatory infiltrates of the lacrimal gland, and the presence of anti-Sjögren's syndrome antigen A and anti-Sjögren's syndrome antigen B antibodies in the serum resemble autoimmune Sjögren's syndrome. These mice develop an ocular surface disorder dry eye that includes disruption of the corneal epithelial layer, corneal edema, and a significant decline in conjuctival goblet cells. Externally, several mice develop dry crusty eyes that eventually close. The inflammatory CD4(+) T cells detected in the lacrimal gland, as well as those in the periphery of older TSP-1 null mice, secrete interleukin-17A, a cytokine associated with chronic inflammatory diseases. Antigen-presenting cells, derived from TSP-1 null, but not from wild-type mice, activate T cells to promote the Th17 response. Together, these results indicate that TSP-1 deficiency results in a spontaneous form of chronic dry eye and aberrant histopathology associated with Sjögren's syndrome.
authors.affiliation: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Turpie
authors.forename: Takeru
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Abha
authors.initials: A
authors.lastname: Gulati
authors.forename: Jose David
authors.initials: JD
authors.lastname: Rios
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Dartt
authors.forename: Sharmila
authors.initials: S
authors.lastname: Masli
mesh_terms: D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D020397:Goblet Cells / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013666:Tears; D019700:Thrombospondin 1 / Q000172:deficiency* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D020381:Interleukin-17; D019700:Thrombospondin 1
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