c-Rel but not NF-κB1 is important for T regulatory cell development

Abstract

Regulatory T (Treg) cells are crucial for maintaining peripheral tolerance and controlling T-cell responses. The generation of Treg in the thymus requires TCR triggering and CD28 costimulation. Engagement of these receptors induces a number of signalling pathways, including the activation of NF-κB via PKCθ and the Bcl-10/CARMA1/MALT complex. Previous studies have shown that PKCθ, Bcl-10 and CARMA1 are important for Treg development. It is unclear, however, whether different members of the NF-κB family contribute to Treg development or homeostasis. In this study, we show that Treg numbers are reduced in the absence of c-Rel but not NF-κB1 (p50). Furthermore, using mixed bone marrow chimeras from WT and KO animals, we demonstrate that the requirement for PKCθ, Bcl-10 and c-Rel is T-cell intrinsic, and cannot be rescued by the presence of WT cells. Therefore, c-Rel and NF-κB1 have differential roles in Treg development. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.