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

• DOI: 10.1126/science.aaz4544
• Publication Date: 2021-03-25T19:24:25Z
• Authors: Ming Liu; Jinyi Zhang; Benjamin D. Pinder; Qingquan Liu; Dingyan Wang; Hao Yao; Yubo Gao; Aras Toker; Jimin Gao; Alan Peterson; Jia Qu; Katherine A. Simi...
• Keywords: Mice, Knockout; Sirolimus; 0301 basic medicine; T-Lymphocytes; TOR Serine-Threonine Kinases; Immunologic Deficiency Syndromes; Receptors, Antigen, T-Cell; Autoimmunity; Cell Differentiation; Regulatory-Associated Protein of mTOR; Lymphocyte Activation; Autoimmune Diseases; Wiskott-Aldrich Syndrome Protein Family; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Rapamycin-Insensitive Companion of mTOR Protein; Animals; Homeostasis; Transcriptome; Proto-Oncogene Proteins c-akt; Signal Transduction

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