Abstract
Oncostatin M (OSM) has been implicated in immune regulation, though its precise role remains elusive. Here we show that OSM plays a crucial role in the prevention of autoimmune diseases. OSM-deficient mice showed normal development of T cells, B cells and DC; however, their thymus showed hypoplasia and altered medullary structure. Autoantibodies against dsDNA accumulated and glomerulonephritis developed in aged OSM-deficient mice. Apoptotic cells accumulated in the thymus of OSM-deficient mice, and the administration of dexamethasone in young OSM-deficient mice resulted in the massive accumulation of apoptotic thymocytes and production of autoantibodies. These results suggest that OSM plays a key role in the prevention of autoimmune disease by regulating the clearance of apoptotic thymocytes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging
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Albuminuria / etiology
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Albuminuria / urine
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Animals
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Antibodies, Antinuclear / blood
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Antibodies, Antinuclear / immunology
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Apoptosis / immunology*
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Autoimmunity / genetics
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Autoimmunity / immunology
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CD4 Antigens / analysis
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Creatinine / urine
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Dexamethasone / pharmacology
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Epithelial Cells / cytology
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Epithelial Cells / metabolism
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Glomerulonephritis / genetics
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Glomerulonephritis / pathology*
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Glomerulonephritis / physiopathology*
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Kidney / pathology
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Macrophages / chemistry
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Macrophages / cytology
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Macrophages / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Oncostatin M / deficiency*
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Oncostatin M / physiology
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Phagocytosis / immunology
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T-Lymphocytes / cytology*
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T-Lymphocytes / drug effects
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Thymus Gland / abnormalities*
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Thymus Gland / physiopathology*
Substances
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Antibodies, Antinuclear
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CD4 Antigens
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Oncostatin M
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Dexamethasone
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Creatinine