SHIP deficiency causes Crohn's disease-like ileitis

Kerr, William G; Park, Mi-Young; Maubert, Monique; Engelman, Robert W

The absence of enteric pathology in SHIP À/À hosts reconstituted with WT BM indicates that SHIP-deficiency does not cause an IEC functional barrier defect leading to ileitis. Conversely, that the CD-like phenotype can be transferred to an immunocompetent host by SHIP-deficient haematopoietic cells suggests that SHIP-deficient ileitis is due to an alteration in the regulation of innate immune functions (eg, granulocytee monocyte responses), a failure of T cell mediated mucosal barrier functions or a combination of such potential alterations. Ileitis in SHIP-deficient mice may result from a deficit in mucosal T cell function that permits inappropriate granulocyteemonocyte responses to commensal organisms and luminal antigens culminating in the inflamed states observed in the ileum of SHIP-deficient mice.