The innate immune system is also involved in the earliest events of CD pathogenesis, through TLRs-downstream activation [18] that, through MyD88 and TRIF-dependent pathways, allows NF-κB to translocate into the cell nucleus and activate transcription of several genes encoding a proinflammatory cascade of cytokines and chemokines. This evidence concerns the gene NFKB1 and Cowden disease.