Dendritic cell apoptosis in the maintenance of immune tolerance.
Apoptosis in the immune system is critical for maintaining self-tolerance and preventing autoimmunity. Nevertheless, inhibiting apoptosis in lymphocytes is not alone sufficient to break self-tolerance, suggesting the involvement of other cell types. We investigated whether apoptosis in dendritic cells (DCs) helps regulate self-tolerance by generating transgenic mice expressing the baculoviral caspase inhibitor, p35, in DCs (DC-p35). DC-p35 mice displayed defective DC apoptosis, resulting in their accumulation and, in turn, chronic lymphocyte activation and systemic autoimmune manifestations. The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance.
Chen
Min
M
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA. minc@bcm.edu
Wang
Yui-Hsi
YH
Wang
Yihong
Y
Huang
Li
L
Sandoval
Hector
H
Liu
Yong-Jun
YJ
Wang
Jin
J
D019264:Adoptive Transfer; D000375:Aging; D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D017209:Apoptosis; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D061945:Caspase Inhibitors; D002470:Cell Survival; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology*; D007668:Kidney / Q000276:immunology; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017634:Self Tolerance; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D000974:Antibodies, Antinuclear; D061945:Caspase Inhibitors; D014764:Viral Proteins; C492234:p35 protein, Baculovirus