It has previously been shown to activate NF-kB dependent TLR4 signaling in cultured mouse CD cell lines, which involves rapid IκB-α degradation [36,37] (Supplementary Figure S1B), as well as in primary CD cells [38] (although additional activation of the non-canonical, TLR4-independent inflammasome pathway cannot be excluded). This evidence concerns the gene NFKB1 and Cowden disease.