Most of the therapeutic strategies in CD are based on systemic immunomodulation or targeting pro-inflammatory cytokines involved in the activation of mucosal TRM cells, such as antibodies against TNFα, IL-12 and/or IL-23, or against integrin α4β7.57 In this context, however, the relationship between AIEC and the dysregulated activation of IL-23/pTh17 axis in CD patients has never been fully characterized. Here, TNF is linked to Cowden disease.