SHIP1 is required for T cell surveillance of occult malignancies

Recent analysis of a human Crohn's disease (CD) cohort revealed a significant subset of patients have severely reduced levels of SHIP1 expression suggesting SHIP1 deficiency leads to CD in both rodents and humans. The mucosal inflammatory disease that causes the premature death of SHIP1-/- mice is a consequence of the requirement of SHIP1 expression for the survival of effector T cells in mucosal tissues.

T cell specific ablation of SHIP1 expression in CD4CreSHIP1flox/flox mice also results in Crohn's disease-like ileitis, but less severe than in their germline SHIP1-/- counterparts due to the absence of a SHIP1 deficient neutrophil compartment. Consequently CD4CreSHIP1flox/flox mice live much longer than their SHIP1-/- counterparts. As Crohn's disease is associated with an increased risk of intestinal cancers in humans and that T cells are proposed to protect from occult malignancies, we hypothesized that CD4CreSHIP1flox/flox mice would develop malignancies originating in the gut.