The complicated role of NF-kappaB in T-cell selection

The nuclear factor (NF)-kappaB transcription factor family plays important roles in the immune system. Aberrant NF-kappaB signaling is frequently associated with inflammation and autoimmune diseases but the underlying mechanisms are not fully understood. Recent studies show that NF-kappaB plays a critical role in T-cell central tolerance. Two NF-kappaB signaling pathways have been identified: the canonical pathway and the alternative pathway. In the establishment of T-cell central tolerance, the alternative pathway appears to be the key signaling component in thymic stromal cells for their development and function, while the canonical pathway exerts its function more in autonomous T-cell selection. This review intends to summarize the current understanding of the role of NF-kappaB in establishing T-cell central tolerance and highlight unsolved intriguing questions for future work.