Mice from a strain that ordinarily develops systemic lupus erythematosus (SLE), but bred with a deficiency in receptor for the protein Interleukin 21, stayed healthy and exhibited none of the symptoms of the disease, researchers at The Jackson Laboratory and National Institutes of Health report.
SLE is an autoimmune disease, with symptoms of varying severity including include painful or swollen joints, unexplained fever and extreme fatigue. An estimated 2 million Americans - 9 out of 10 of them female - live with SLE.
The primary job of the immune system is to identify and vanquish potentially dangerous infectious pathogens. Autoimmune diseases develop when immune system instead unleashes this potent defense system against the individual's own tissues, with predictably severe consequences.
Unlike other autoimmune diseases such as Type 1 diabetes, in which the immune response is focused on certain tissues, SLE is a systemic disease in which abnormal antibodies are produced that injure a variety of tissues and organs, including the skin, heart, lungs and kidneys.
The cause of SLE is not well understood, but recent work by a Jackson Laboratory research team led by Professor Derry Roopenian is shedding light on how the disease develops and offers hope for better therapies.
Interleukin 21 (IL21) is produced as part of the response by immune cells known as T cells. The IL21 produced then affects a variety of cells in the normal immune system response. However, IL21 produced in overabundance by individuals susceptible to SLE can cause the defense mechanism to misfire and produce antibodies that attack the individual's own tissues.
Dr. Roopenian and colleagues at the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases worked with a mouse model for SLE and demonstrated that IL21 signaling is essential for the SLE-like autoimmune disease to progress. Mice deficient in the cellular receptor for IL21 that were otherwise genetically identical remained healthy and exhibited none of the disease symptoms.
"The findings provide strong clue towards understanding how SLE occurs and a clear indication of the importance of Interleukin 21 signaling in lupus like diseases", Dr. Roopenian says. "They suggest that interrupting Interleukin 21 signaling events may prove to be an effective therapeutic option for human SLE."