TNF and Cowden disease: Importantly, we observed a marked decrease in TNF-α production in response to stimulation with the TLR1/2 ligand Pam3CSK4, the TLR2/6 ligand FSL1, and the NOD2 ligand MDP (Figures 4E, G, H). The decreased response to MDP holds particular significance for IBD, as mutations of CARD15/NOD2 have been linked to CD (11).