TNFα blockade inhibits T cell cycling by NOTCH-1 signaling

Introduction: Therapeutic TNFα blockade, such as infliximab (IFX) or adalimumab (ADA) is gaining acceptance in inflammatory diseases, such as Crohn's disease (CD) and ulcerative colitis (UC). However, induction of apoptosis is not an obligation for TNFα inhibitors to act. Thus, further mechanisms of action for TNFα inhibitors must be uncovered. Methods: Mononuclear cells (PBMC) from control, CD, and UC patients were activated by anti-CD3 antibodies and cultured with IFX or ADA. To examine signaling pathways, cells were cultured in the presence of TACE inhibitors (TAPI), TNFα receptor antibodies, and Notch ligand…