Inhibiting IL-21 Signaling Prevents Systemic Lupus Erythematosus

A recent publication linked the development of systemic lupus erythematosus (SLE) in a mouse model to the signaling activity of the cytokine interleukin-21 (IL-21).

SLE is a chronic autoimmune inflammatory connective-tissue disorder characterized by the production of abnormal antibodies that attack and injure joints, kidneys, mucous membranes, and blood vessel walls.

To develop an understanding of the underlying causes of SLE, investigators at The Jackson Laboratory (Bar Harbor, ME, USA) and the [U.S.] National Institutes of Health (Bethesda, MD, USA) conducted a series of experiments using the BXSB-Yaa mouse SLE model. In this study, the investigators were especially interested in pinning down the role of IL-21, which is overexpressed in humans susceptible to SLE. To this end, they genetically engineered a variant of BXSB-Yaa mice that lacked the gene for the IL-21 receptor, which prevented IL-21 signaling in these animals.

Results published in the January 21, 2009, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS) revealed that IL-21 receptor deficient mice failed to develop SLE. On close examination, these animals were found not to display the abnormalities characteristic of SLE, which are seen in normal BXSB-Yaa mice. These included hypergammaglobulinemia, autoantibody production, reduced frequencies of marginal zone B cells and monocytosis, renal disease, and premature morbidity.

"The findings provide a strong clue towards understanding how SLE occurs and a clear indication of the importance of interleukin-21 signaling in lupus like diseases," said senior author Dr. Derry Roopenian, professor of immunology at The Jackson Laboratory. "They suggest that interrupting interleukin-21 signaling events may prove to be an effective therapeutic option for human SLE."

Related Links:
The Jackson Laboratory
National Institutes of Health