[An impaired detection and clearance of dying cells can lead to the development of chronic autoimmunity].
Not properly cleared dead cells are dangerous for the body. The dead cells accumulate, lose their membrane integrity, danger signals are released, and nuclear antigens get accessible in an inflammatory context. In times of increased apoptosis, tolerance can be broken, a chronic inflammation results which then can lead to an autoimmune reaction against nuclear constituents. An impaired clearance of dying cells represents a central pathogenic process in the development of chronic autoimmune diseases like in systemic lupus erythematosus (SLE). Many adaptor molecules and receptors are involved in the clearance of dying cells. Complement components, serum DNase I, phosphatidylserine, and modified glycoproteins participate crucially in the clearance of apoptotic and necrotic cells. We further observed intrinsic defects of macrophages of some SLE patients. Macrophages as well as granulocytes of some SLE patients showed heterogeneous clearance defects. Furthermore, we observed an accumulation of nuclear material in germinal centres of lymph nodes of some SLE patients. The non-ingested nuclear material may provide survival signals for autoreactive B cells and consecutively antinuclear autoantibodies (ANA) will be produced. We therefore conclude that drugs promoting the phagocytosis are important candidates of specific therapies in the future which expect a more gentle and purposive treatment of patients with SLE.
Munoz
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LE
Institut für Klinische Immunologie, Medizinische Klinik 3, Friedrich-Alexander Universität Erlangen-Nürnberg, Glückstrasse 4 a, 91054 Erlangen, Germany.
Herrmann
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M
Gaipl
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US
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D002908:Chronic Disease; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology*; D018448:Models, Immunological; D009336:Necrosis / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*