WAVE2 suppresses mTOR activation to maintain T cell homeostasis and prevent autoimmunity

Abstract

WAVE-ing T cell activation off The WAVE regulatory complex (WRC) is a pentameric complex that regulates actin cytoskeleton dynamics. The precise role for the WRC in immunity has not been established, although recent work has implicated WRC components such as HEM1 in certain human immunodeficiencies. Liu et al. characterized mice with a conditional knockout of the WRC constituent WAVE2 (see the Perspective by Hambleton). These mice exhibited progressive severe autoimmune and inflammatory disease associated with the activation and accelerated differentiation of T cells. WAVE2's suppression of T cell activation was not mediated by the T cell receptor but rather by its inhibition of mammalian target of rapamycin (mTOR) binding to RAPTOR and RICTOR. Accordingly, the autoimmune phenotype of these mice could be ameliorated by pharmacological inhibitors of mTOR signaling. Science , this issue p. eaaz4544 ; see also p. 1309