SLE is a systemic autoimmune disease that affects ~3% of the world’s population and is gender biased, affecting 9 times more women than men1, 2 . Although the milder forms of SLE can be controlled with immunosuppressive drugs, such as corticosteroids, there is no effective treatment for severe disease. Furthermore, studies have found that SLE patients have an increased risk of developing certain types of cancer, particularly non-Hodgkin lymphoma, Hodgkin’s lymphoma, lung and cervical cancer3 . The use of immunosuppressant drugs has been found to be associated with cervical dysplasia4 , suggesting that increased susceptibility to certain cancers may be linked to the immunosuppression. Hence, there is a need to identify novel SLE-related targets for the development of improved therapies.
The NF-κB family of transcription factors is critically involved in the maintenance of a normal immune system, regulating inflammatory genes and immune response. This has led to the hypothesis that deregulation of NF-κB signaling may play a role in the development of autoimmune disease pathology. Indeed, increased activation of NF-κB has been reported in tissues affected by certain autoimmune diseases5 . Current SLE therapies dampen the activity of the entire NF-κB system and hence frequently cause adverse side effects, such as immune-suppression.
We have examined the roles of individual NF-κB family members (specifically NF-κB1, NF-κB2, and c-Rel) in the development and progression of SLE in the Faslpr/lpr mutant mouse model, which develops progressive lymphadenopathy as well as auto-antibody mediated kidney disease. We found that loss of c-Rel resulted in a substantial amelioration of all markers of autoimmunity tested and a dramatic increase in the survival of Faslpr/lpr mice. These findings reveal important insights into the potential targeting of c-Rel in SLE and possibly other autoimmune diseases.