TRAF-STOPping atherosclerosis: targeting of CD40-induced TRAF6 signaling in macrophages reduces (established) atherosclerosis

Inhibition of the costimulatory CD40-CD40L receptor/ligand dyad drastically reduces atherosclerosis. However, its long-term blockage can result in immune suppression. We recently identified small molecule inhibitors that block the interaction between CD40 and TNF Receptor Associated Factor (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, thereby preserving CD40-mediated immunity. Here we further characterized the working mechanisms of TRAF-STOPs 6877002 and 6860766 in atherogenesis.

9

Seijkens TTP, van Tiel CM, Kusters PJH, Atzler D, Soehnlein O, Zarzycka B, Aarts SABM, Lameijer M, Gijbels MJ, Beckers L, den Toom M, Slütter B, Kuiper J, Duchene J, Aslani M, Megens RTA, van 't Veer C, Kooij G, Schrijver R, Hoeksema MA, Boon L, Fay F, Tang J, Baxter S, Jongejan A, Moerland PD, Vriend G, Bleijlevens B, Fisher EA, Duivenvoorden R, Gerdes N, de Winther MPJ, Nicolaes GA, Mulder WJM, Weber C, Lutgens E