Role of apoptosis in autoimmunity.
Apoptosis is a physiological form of cell death required to ensure that the rate of cell division is balanced by the rate of cell death in multicellular organisms. Dysregulation of apoptosis is associated with the pathogenesis of a wide array of diseases: cancer, neurodegeneration, autoimmunity, heart disease and others. In this review we collect arguments supporting a hypothesis of a dysregulated apoptosis leading to development of autoimmunity like systemic lupus erythematosus (SLE). This notion is supported by occurence of known autoantigens in apoptotic blebs, in vitro findings of an increased rate of apoptotic lymphoblasts despite optimal cytokine stimulation combined with a defective in vitro clearance of apoptotic bodies by SLE phagocytes. Moreover, we and others could generate histone-specific lymphocytic cell lines from cells after activation with autologous apoptotic material. These lymphocytes could stimulate autologous B-lymphocytes to produce of anti-dsDNA antibodies, a diagnostic hallmark for SLE. Finally, antibodies against phospholipids like phosphatidylserine are often associated with systemic autoimmunopathies like SLE and others. Phosphatidylserine is exposed on apoptotic cells as early sign of programmed cell death and serves as phagocyte recognition molecule for apoptotic cells. Formation of immune complexes and deposition in tissues might lead to organ damage and disease. This scenario will be discussed in this review in detail.
Institute of Clinical Immunology and Rheumathology, Medical Department III, University of Erlangen-Nuremberg, Germany.
H M
HM
Lorenz
M
M
Herrmann
T
T
Winkler
U
U
Gaipl
J R
JR
Kalden
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity / Q000502:physiology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology*