SHIP deficiency causes Crohn's disease-like ileitis

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

The above studies show that ileitis occurs in germline SHIP mutant mice, indicating this CD-like pathology may have a developmental origin. To test this possibility we analysed intestinal pathology in MxCreSHIP flox/flox mice where SHIP expression is normal in fetal, neonatal and adolescent life, but can be ablated during adulthood following polyI/C administration. 33 This approach results in eosinophilic crystalline pneumonia in adult mice rendered SHIP deficient. 49 For this analysis twelve 6e8 week old MxCreSHIP flox/flox mice and twelve SHIP flox/flox controls, each of both sexes were submitted to comparable histopathological analyses. Primary gastrointestinal lesions were present only within the ileum of MxCreSHIP flox/flox mice, while SHIP flox/flox mice were unaffected 4e5 weeks after the last injection of polyI/C. Of the 12 MxCreSHIP flox/flox mice evaluated, only 1 (8%) lacked ileitis, while 11 of 12 (92%) developed ileitis with a mean inflammatory grade of 3.561.9. Comparable to ileitis of SHIP À/À and SHIP DIP/DIP mice, ileitis of MxCre SHIP flox/flox mice was segmental in nature with mixed inflammatory cell infiltrations. Granuloma formation was evident in 2 of 12 (17%) of MxCreSHIP flox/flox mice. Thus, CD-like ileitis develops with selective deletion in adult mice, illustrating that SHIP expression is required to maintain normal mucosal immune homeostasis and regulation in the adult ileum.