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The Alzheimer’s Disease-Associated Protein BACE1 Modulates T Cell Activation and Th17 Function

Hernandez-Mir, G;Raphael, I;Revu, S;Poholek, CH;Avery, L;Hawse, WF;Kane, LP;McGeachy, MJ;

-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is best known for its role in Alzheimer’s disease amyloid plaque formation but also contributes to neurodegenerative processes triggered by CNS injury. In this article, we report that BACE1 is expressed in murine CD4+ T cells and regulates signaling through the TCR. BACE1-deficient T cells have reduced IL-17A expression under Th17 conditions and reduced CD73 expression in Th17 and inducible T regulatory cells. However, induction of the Th17 and T regulatory transcription factors RORt and Foxp3 was unaffected. BACE1-deficient T cells showed impaired pathogenic function in experimental autoimmune encephalomyelitis. These data identify BACE1 as a novel regulator of T cell signaling pathways that impact autoimmune inflammatory T cell function. Copyright 2019 by The American Association of Immunologists, Inc.