Spotlight on Research 2011

May 2011 (historical)

Study Shows Unexpected Role of Immune Cell in Lupus

A new study by NIAMS-supported researchers provides surprising insights into the immune process involved in lupus, a chronic inflammatory disease that can damage many parts of the body including the joints, skin, kidneys, heart, lungs, blood and brain. The studyís findings, which focus on an immune system cell called a dendritic cell, could potentially lead to the development of new treatments for the disease, the researchers say.

In infectious disease models, dendritic cells are important for activating two other types of immune system cells, T cells and B cells, as part of the response to invaders such as viruses and bacteria. But the role they play in autoimmune diseases such as lupus is unclear.

To better understand that role, researchers led by Mark Shlomchik, M.D., Ph.D., professor of laboratory medicine and of immunology at Yale University School of Medicine in New Haven, CT, developed and used a mouse model of lupus genetically manipulated to lack dendritic cells. Without dendritic cells, the investigators demonstrated that overall disease in the lupus prone-mice was reduced dramatically. Furthermore, they showed that mice lacking dendritic cells were less likely to develop characteristic kidney and skin disease.

While this finding confirmed that dendritic cells do play an important part in disease progression, the scientists were surprised that the removal of the dendritic cells did not hinder the initial activation of the other immune system cells, says Dr. Shlomchik. Instead, dendritic cells were essential for the invasion of target organs by inflammatory cells, including T cells, and responsible for tissue damage. In other words, instead of initiating the immune response, the dendritic cells amplified it, says Dr. Shlomchik.

While current lupus therapies are directed largely toward T cells and B cells, the new research, published in the journal Immunity, suggests therapies targeted at blocking dendritic cells may be effective at reducing or preventing tissue damage in lupus and perhaps other autoimmune diseases.

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 Servicesí 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 NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.

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Teichmann LL, Ols ML, Kashgarian M, Reizis B, Kaplan DH, Shlomchik MJ. Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage. Immunity. 2010 Dec 14; 33(6): 967-78.