Apoptosis and autoimmune disease
- Keith Elkon, MD
Keith Elkon, MD
- Mannik-Henderson Professor of Medicine
- Head, Division of Rheumatology
- University of Washington
Apoptosis refers to cell death that occurs in a programmed manner, is characterized by cellular condensation, and is noninflammatory. By all of these criteria, it differs from necrosis, which is often referred to as "accidental" or pathologic death and which is accompanied by cell swelling and inflammation.
Apoptosis plays a pivotal role in the following processes [1,2]:
●Morphogenesis and tissue remodeling during embryonic development
●Cell death associated with homeostasis (eg, immune system, lungs, gastrointestinal tract)
●Elimination of immune effector cells that proliferate in response to activation (eg, by microbial infection)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Vaux DL, Korsmeyer SJ. Cell death in development. Cell 1999; 96:245.
- Nagata S. Apoptosis by death factor. Cell 1997; 88:355.
- Savill J, Dransfield I, Gregory C, Haslett C. A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2002; 2:965.
- Erwig LP, Henson PM. Immunological consequences of apoptotic cell phagocytosis. Am J Pathol 2007; 171:2.
- Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008; 451:1069.
- Horvitz HR. Genetic control of programmed cell death in the nematode Caenorhabditis elegans. Cancer Res 1999; 59:1701s.
- Reddien PW, Horvitz HR. The engulfment process of programmed cell death in caenorhabditis elegans. Annu Rev Cell Dev Biol 2004; 20:193.
- Parrish AB, Freel CD, Kornbluth S. Cellular mechanisms controlling caspase activation and function. Cold Spring Harb Perspect Biol 2013; 5.
- Los M, Wesselborg S, Schulze-Osthoff K. The role of caspases in development, immunity, and apoptotic signal transduction: lessons from knockout mice. Immunity 1999; 10:629.
- Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell 2004; 116:205.
- Newmeyer DD, Ferguson-Miller S. Mitochondria: releasing power for life and unleashing the machineries of death. Cell 2003; 112:481.
- Aravind L, Dixit VM, Koonin EV. The domains of death: evolution of the apoptosis machinery. Trends Biochem Sci 1999; 24:47.
- Peter ME, Krammer PH. The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 2003; 10:26.
- Ashkenazi A, Dixit VM. Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 1999; 11:255.
- Cory S, Huang DC, Adams JM. The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene 2003; 22:8590.
- Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9:47.
- Riedl SJ, Shi Y. Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 2004; 5:897.
- Downward J. PI 3-kinase, Akt and cell survival. Semin Cell Dev Biol 2004; 15:177.
- Mevorach D, Mascarenhas JO, Gershov D, Elkon KB. Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 1998; 188:2313.
- Gershov D, Kim S, Brot N, Elkon KB. C-Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 2000; 192:1353.
- Anderson HA, Maylock CA, Williams JA, et al. Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol 2003; 4:87.
- Nagata S, Hanayama R, Kawane K. Autoimmunity and the clearance of dead cells. Cell 2010; 140:619.
- Baumann I, Kolowos W, Voll RE, et al. Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum 2002; 46:191.
- Elkon KB. Cell survival and death in rheumatic diseases. In: Kelley's Textbook of Rheumatology, 9th ed, Firestein G, Budd R, Gabriel S, et al (Eds), Elsevier Publishing, Philadelphia 2012. p.382.
- Dwivedi N, Radic M. Citrullination of autoantigens implicates NETosis in the induction of autoimmunity. Ann Rheum Dis 2014; 73:483.
- Linkermann A, Green DR. Necroptosis. N Engl J Med 2014; 370:455.
- Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med 2013; 5:178ra40.
- Lood C, Blanco LP, Purmalek MM, et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat Med 2016; 22:146.
- Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 2009; 7:99.
- Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998; 392:86.
- Ganguly D, Haak S, Sisirak V, Reizis B. The role of dendritic cells in autoimmunity. Nat Rev Immunol 2013; 13:566.
- Utz PJ, Anderson P. Posttranslational protein modifications, apoptosis, and the bypass of tolerance to autoantigens. Arthritis Rheum 1998; 41:1152.
- Hall JC, Casciola-Rosen L, Rosen A. Altered structure of autoantigens during apoptosis. Rheum Dis Clin North Am 2004; 30:455.
- Colonna L, Lood C, Elkon KB. Beyond apoptosis in lupus. Curr Opin Rheumatol 2014; 26:459.
- Barrat FJ, Elkon KB, Fitzgerald KA. Importance of Nucleic Acid Recognition in Inflammation and Autoimmunity. Annu Rev Med 2016; 67:323.
- Russell AI, Cunninghame Graham DS, Shepherd C, et al. Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. Hum Mol Genet 2004; 13:137.
- Manderson AP, Botto M, Walport MJ. The role of complement in the development of systemic lupus erythematosus. Annu Rev Immunol 2004; 22:431.
- International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley JB, Alarcón-Riquelme ME, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 2008; 40:204.
- Granville DJ, Carthy CM, Yang D, et al. Interaction of viral proteins with host cell death machinery. Cell Death Differ 1998; 5:653.
- van Venrooij WJ, van Beers JJ, Pruijn GJ. Anti-CCP Antibody, a Marker for the Early Detection of Rheumatoid Arthritis. Ann N Y Acad Sci 2008; 1143:268.
- Kobayashi T, Okamoto K, Kobata T, et al. Apomodulation as a novel therapeutic concept for the regulation of apoptosis in rheumatoid synoviocytes. Curr Opin Rheumatol 1999; 11:188.
- Scatizzi JC, Hutcheson J, Pope RM, et al. Bim-Bcl-2 homology 3 mimetic therapy is effective at suppressing inflammatory arthritis through the activation of myeloid cell apoptosis. Arthritis Rheum 2010; 62:441.
- Sgonc R, Gruschwitz MS, Dietrich H, et al. Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma. J Clin Invest 1996; 98:785.
- Sgonc R, Gruschwitz MS, Boeck G, et al. Endothelial cell apoptosis in systemic sclerosis is induced by antibody-dependent cell-mediated cytotoxicity via CD95. Arthritis Rheum 2000; 43:2550.
- Tan FK, Zhou X, Mayes MD, et al. Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients. Rheumatology (Oxford) 2006; 45:694.
- Duan H, Fleming J, Pritchard DK, et al. Combined analysis of monocyte and lymphocyte messenger RNA expression with serum protein profiles in patients with scleroderma. Arthritis Rheum 2008; 58:1465.