Inflammatory bowel diseases
Signaling networks perpetuating chronic inflammatory bowel diseases remain unclear. Here we report that key players of the IL-7 pathway as well as α4/β7 gut-homing integrins accumulate in diseased colon biopsies. While in mice IL-7 is known to play a role in systemic inflammation, we found that IL-7, specifically in humans, also controls α4/β7 integrin expression and imprints gut-homing specificity on T cells. IL-7 receptor blockade reduced human T cell homing to the gut and colon inflammation in different humanized mouse models of colitis and reduced ex-vivo production of IFNγ by tissues punched from ulcerative colitis patients. In addition, transcriptional analysis of diseased colon mucosa indicated that IL-7 receptor signaling pathway discriminated response to conventional therapies. Our findings suggest that resistance to treatment in inflammatory bowel diseases may occur at least in part by dysregulated IL-7 receptor signaling pathway and point IL-7 as a fuel for gut chronic inflammation.