TNFR2-IL-17RD heteromerization reveals a novel mechanism for NF-{kappa}B activation [Signal Transduction]

November 5th, 2014 by Yang, S., Wang, Y., Mei, K., Zhang, S., Sun, X., Ren, F., Liu, S., Yang, Z., Wang, X., Qin, Z., Chang, Z.

TNF receptor 2 (TNFR2) exerts diverse roles in the pathogenesis of inflammatory and autoimmune diseases. Here, we report that TNFR2 but not TNFR1 forms a heteromer with IL-17RD, also named Sef, to activate NF-κB signaling. TNFR2 associates with IL-17RD, leading to mutual receptor aggregation and TRAF2 recruitment, which further activate the downstream cascade of NF-κB signaling. Depletion of IL-17RD impaired TNFR2-mediated activation of NF-κB signaling. Importantly, IL-17RD was markedly increased in renal tubular epithelial cells (RTECs) in nephritis rats, and a strong interaction of TNFR2 and IL-17RD was observed in the renal epithelia. The IL-17RD-TNFR2 complex in activation of NF-κB may explain the role of TNFR2 in inflammatory diseases including nephritis.