Breakthrough in Lupus Research

researchers were able to reduce symptoms of lupus in mice by eliminating a key immune system cell and in doing so may have identified a new therapeutic target for a variety of other autoimmune diseases.

The findings, reported in the Dec. 16 issue of the journal Immunity, focused on the role the dendritic cell plays in systemic lupus erythematosus or SLE.

The chronic inflammatory disease affects a variety of parts of the body including skin, joints, blood, and kidneys. According to the Lupus Foundation of America, “1.5 million Americans, and at least five million people worldwide, have a form of lupus.” Additionally:

• Women make up 90% of individuals diagnosed with the disease.
• Most people will develop lupus between the ages of 15-44.
• Systemic lupus accounts for approximately 70% of all cases of lupus. In approximately half of these cases, a major organ, such as the heart, lungs, kidneys or brain, will be affected.
• Cutaneous lupus (affecting only the skin) accounts for approximately 10% of all lupus cases.
• Drug-induced lupus accounts for about 10% of all lupus cases and is caused by high doses of certain medications.

Dendritic cells are important for initiating the immune response to pathogens but it is unclear what role they play in autoimmune diseases, such as SLE.

A team led by Mark Shlomchik, professor of Laboratory Medicine and of Immunobiology and senior author of the paper, knocked out dendritic cells in lupus-prone mice and found a dramatic reduction in symptoms of lupus. They also discovered another surprise.

Dendritic cells were believed to be crucial in activating T cells, which along with B cells comprise the two main arms of the immune system. However, knocking out the dendritic cells in lupus mice did not reduce the activation of pathogenic T cells as expected. Instead, the cells disappeared from inflamed tissue such as kidneys, causing a reduction in symptoms in lupus mice lacking the dendritic cells. Dendritic cells appear to play a localized role in lupus tissue damage and so might make a good therapeutic target for lupus and possibly other autoimmune diseases as well, the authors say.

“Dendritic cells could be having the same effects in a variety of other autoimmune diseases, but we will not know until we do similar experiments in other disease models,” Shlomchik said, in a press release.

Other Yale authors of the paper are Lino Teichmann, Michael Kashgarian, and Michelle Harris-Ols.

The work was funded by the National Institute of Arthritis and Musculoskeletal Diseases and the Lupus Research Institute.

Source: Yale University

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