Apoptosis inhibitor expressed by macrophages tempers autoimmune colitis and the risk of colitis-based carcinogenesis in TCRα-/- mice

Background Crohn's disease and ulcerative colitis (UC) are the two main entities involved in human inflammatory bowel disease (IBD). However, their precise etiologies remain unclear. To study the development of mucosal inflammation, and chronic inflammation-based dysplasia and carcinoma formation, we examined possible roles of the apoptosis inhibitor expressed by macrophages ( AIM) in an experimental IBD model. Methods In this study, we used T cell receptor a deficient (TCR alpha(-/-)) mice, a known UC-like colitis model. We generated TCR alpha(-/-) x AIM(-/-) double knockout mice by crossbreeding TCR alpha(-/-) with AIM(-/-) mice. At 24 weeks of age, mice were killed to obtain colon tissues for pathological wxaminations. TCR alpha(-/-) x AIM(+/-) mice, heterozygous littermates of TCR alpha(-/-) x AIM(-/-) mice, were used as controls. Results Severe colitis was observed in TCR alpha(-/-) x AIM(-/-)mice, when compared with TCR alpha(-/-) x AIM(+/-) mice. Dysplasia was detected in TCR alpha(-/-) x AIM(-/-) mice, but not in TCR alpha(-/-) x AIM(+/-) mice. Adenocarcinoma formation was observed from dysplasia only in TCR alpha(-/-) x AIM(-/-) mice. Conclusion Not only a high incidence of severe colitis but also dysplasia and adenocarcinoma formation were observed in TCR alpha(-/-) x AIM(-/-) mice only. AIM have some regulatory roles in inflammation and progression of dysplasia to carcinoma in TCR alpha(-/-) mice.