The lineage specific transcription factor Foxp3 is required for many of the immune suppressive functions of Regulatory T cells (Tregs), however Foxp3 also serves a wider role by stabilising the overall transcriptional landscape in these cells founded by other transcription factors (1). Amongst the transcription factors implicated in the differentiation of Tregs during thymic development are the canonical NF-kB proteins cRel and RelA (2). The NF-kB family of transcription factors also play crucial roles in the function of mature conventional CD4+ and CD8+ T cells, NKT cells, B cells and myκeloid cells, but whether NF-kB transcription factors also function in Tregs following the completion of their development is currently unclear. To determine if the NF-kB protein RelA plays a role in Treg function following development, we established a mouse model in which Foxp3+ cells are selectively deficient for RelA (relaΔFoxp3cre). Despite preserving normal Tregs numbers, we report here that relaΔFoxp3cre mice develop autoimmune disease after six weeks of age that involves profound lymphadenopathy and immune cell infiltration detected in various organs. This is accompanied by excessive B and T lymphocyte activation, increased serum cytokine levels, autoantibody production and damage to various tissues. Collectively, this study shows that that expression of RelA in murine Tregs is required to prevent the development of autoimmune disease.