Bcl-3 regulates T cell function through energy metabolism

Abstract

Abstract Background: Bcl-3 is a member of the IκB protein family and an essential nuclear factor NF-κB activity modulator. It is well established that Bcl-3 is critical for the normal development, survival and differentiation of adaptive immune cells, especially T cells. However, the regulation of immune cell function by Bcl-3 through metabolic pathways has rarely been studied. Results: In this study, we explored the role of Bcl-3 on the metabolism and function of T cells through the mTOR pathway. We verified that the proliferation of Bcl-3-deficient Jurkat T cells was inhibited, but its activation was promoted, and Bcl-3 depletion regulated the cellular energy metabolism by reducing intracellular ATP and ROS production levels and mitochondrial membrane potential. Bcl-3 also regulates cellular energy metabolism in naive CD4+ T cells. In addition, the knockout of Bcl-3 altered the expression of mTOR, Akt, and Raptor, genes related to metabolism in Jurkat cells. Conclusions: This finding indicates that Bcl-3 may mediate the energy metabolism of T cells through the mTOR pathway, thereby affecting their function. Overall, we provide novel insights into the regulatory role of Bcl-3 on T-cell energy metabolism for prevention and treatment strategies of immune diseases.