Immune deficiency or hyperactivity-Nf-kappab illuminates autoimmunity

Nuclear factor (NF)-kappaB is a transcription factor family which transmits signals from the cell surface to the nucleus, resulting in transcriptional effects on genes involved in inflammation, cell differentiation and survival. The signaling of NF-kappaB and mitogen-activated protein (MAP) kinases through adapter molecules is of critical importance to survival and activation of all cells in the body, including those regulating innate and adaptive immunity. Here we review the individual and intersecting roles played by the alternate and classical NF-kappaB pathways in the pathogenesis of autoimmune disease. Understanding the differences in classical and alternate NF-kappaB function has greatly assisted the development of models of their contribution to different autoimmune diseases. To exemplify these concepts, we consider the contribution of NF-kappaB to rheumatoid arthritis and type 1 diabetes pathogenesis and approaches to immunotherapy.