Survival and maintenance of regulatory T cells require the kinase TAK1

Abstract

Regulatory T (Treg) cells play a central role in regulating peripheral immune tolerance and preventing autoimmunity. Despite the extensive studies on the development of Treg cells, the molecular mechanisms that maintain the population of committed Treg cells remain poorly understood. We show here that Treg-conditional ablation of the kinase TAK1 reduced the number of Treg cells in the peripheral lymphoid organs, causing abnormal activation of conventional T cells and autoimmune symptoms. Using an inducible gene knockout approach, we further demonstrate that TAK1 is crucial for the survival of Treg cells. Expression of a constitutively active B kinase partially restored the level of Treg cells in the TAK1Treg-KO mice. These results suggest a crucial role for TAK1 for maintaining the survival of committed Treg cells under physiological conditions.