The removal of cells that die during apoptosis—the biological process of programmed cell death—has, for some time, been known to be involved in the development of autoimmune diseases like systemic lupus erythematosus (lupus), an inflammatory disorder that affects multiple organ systems. Recently, with partial support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), scientists at the University of Washington in Seattle have provided an explanation for why mice, genetically modified to lack an apoptosis-linked protein, develop an autoimmune disease similar to lupus. The study was reported in The Journal of Clinical Investigation.
Lupus can affect many parts of the body, including the kidneys, skin, heart and blood vessels, lungs, and the brain. Some of the disease’s most common symptoms include painful or swollen joints, unexplained fever, rashes, and extreme fatigue.
In healthy individuals, immune cells called phagocytes envelop dead cells and remove them without triggering inflammation or other adverse immune reactions. A protein called MFG-E8 signals phagocytes to surround and ingest apoptotic cells. In people with lupus, however, apoptotic cells are not properly cleared, causing the immune system to attack the body’s own cells. University of Washington researchers YuFeng Peng, Ph.D., and Keith B. Elkon, M.D., studied mice lacking MFG-E8, and found that, not only are their phagocytes slower to take up apoptotic cells, but they also process the dead cells differently after they have engulfed them. These changes in degrading the apoptotic debris within the phagocytes, say the investigators, result in the activation of immune cells like T cells that can cause autoimmune conditions to occur.
The information that Drs. Peng and Elkon have uncovered could help form the basis of new therapeutic approaches to autoimmune diseases like lupus. "We don’t yet know all the specifics of how apoptotic cells and their debris are processed in lupus," says Dr. Peng, "but our work may be pointing us to potential new treatment targets."
Partial support for this study was also provided by the Arthritis Foundation.The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at https://www.niams.nih.gov.
Peng Y, Elkon KB. Autoimmunity in MFG-E8-deficient mice is associated with altered trafficking and enhanced cross-presentation of apoptotic cell antigens. J Clin Invest. 2011 Jun 1;121(6):2221-41. PubMed PMID: 21537078.