Deltex1: a novel regulator of T cell activation and T cell anergy (84.12)

Abstract

Abstract Deltex1 (DTX1) is a target of Notch signaling, but its physiological function in T cells is unclear. Here we show that Dtx1 is a novel transcription target of NFAT involved in T cell anergy. DTX1 was upregulated during both in vitro and in vivo T cell anergy induction. Transgenic expression of Dtx1 attenuated T cell activation but does not alter T cell development. DTX1 transgenic mice were resistant to EAE induction. In the present study, we generated DTX1-deficient mice to study the function of DTX1 in T cell anergy and T cell development. Dtx1 knockout did not interfere with thymocyte development. Deficiency of DTX1 augmented T cell activation, conferred resistance to anergy induction, enhanced autoantibody generation, and increased inflammation and autoimmunity. DTX1 therefore represents an interactive component downstream of calcium/NFAT that regulates T cell anergy.