It is known that (1) downstream signal transduction molecules, including I-κB and NF-κB, are shared by the IL-17 and TNF-α signaling pathways [8–10], (2) IL-17R knock-out mice are protected from inflammatory diseases including CD [27], and (3) TRAF3IP2-deficient mice are protected against dextran sodium sulfate-induced colitis, which presents with IBD-like manifestations [28]. Here, TNF is linked to Cowden disease.