Nuclear factor-κB in immunity and inflammation: The Treg and Th17 connection

Abstract

Although nuclear factor-κB (NF-κB) is generally considered to be a pro-inflammatory transcription factor, recent studies indicate that it also plays a critical role in the development of an anti-inflammatory T cell subset called regulatory T (Treg Treg ) cells. Two NF-κB proteins, c-Rel c-Rel and p65, drive the development of Treg Treg cells by promoting the formation of a Foxp3-specific enhanceosome. Consequently, c-Rel c-Rel -deficient mice have marked reductions in Treg Treg cells, and c-Rel c-Rel -deficient T cells are compromised in Treg Treg cell differentiation. However, with the exception of Foxp3, most NF-κB target genes in immune cells are pro-inflammatory. These include several Th17 Th17 -related cytokine genes and the retinoid-related orphan receptor-γ (Rorg or Rorc) that specifies Th17 Th17 differentiation and lineage-specific function. T cells deficient in c-Rel c-Rel or p65 are significantly compromised in Th17 Th17 differentiation, and c-Rel c-Rel -deficient mice are defective in Th17 Th17 responses. Thus, NF-κB is required for the development of both anti-inflammatory Treg Treg and pro-inflammatory Th17 Th17 cells.