Oncostatin M deficiency leads to thymic hypoplasia, accumulation of apoptotic thymocytes and glomerulonephritis.
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.
Esashi
Eiji
E
Institute of Molecular and Cellular Biosciences, University of Tokyo Bunkyo-ku, Tokyo, Japan.
Ito
Hiroaki
H
Minehata
Ken-ichi
K
Saito
Shigeru
S
Morikawa
Yoshihiro
Y
Miyajima
Atsushi
A
D000375:Aging; D000419:Albuminuria / Q000209:etiology / Q000652:urine; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D003404:Creatinine / Q000652:urine; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005921:Glomerulonephritis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053683:Oncostatin M / Q000172:deficiency* / Q000502:physiology; D010587:Phagocytosis / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D013950:Thymus Gland / Q000002:abnormalities* / Q000503:physiopathology*
D000974:Antibodies, Antinuclear; D015704:CD4 Antigens; D053683:Oncostatin M; D003907:Dexamethasone; D003404:Creatinine