Apoptosis inhibitor expressed by macrophages tempers autoimmune colitis and the risk of colitis-based carcinogenesis in TCRalpha-/- 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 alpha deficient (TCRalpha(-/-)) mice, a known UC-like colitis model. We generated TCRalpha(-/-) x AIM(-/-) double knockout mice by crossbreeding TCRalpha(-/-) with AIM(-/-) mice. At 24 weeks of age, mice were killed to obtain colon tissues for pathological examinations. TCRalpha(-/-) x AIM(+/-) mice, heterozygous littermates of TCRalpha(-/-) x AIM(-/-) mice, were used as controls.
RESULTS: Severe colitis was observed in TCRalpha(-/-) x AIM(-/-) mice, when compared with TCRalpha(-/-) x AIM(+/-) mice. Dysplasia was detected in TCRalpha(-/-) x AIM(-/-) mice, but not in TCRalpha(-/-) x AIM(+/-) mice. Adenocarcinoma formation was observed from dysplasia only in TCRalpha(-/-) x AIM(-/-) mice.
CONCLUSION: Not only a high incidence of severe colitis but also dysplasia and adenocarcinoma formation were observed in TCRalpha(-/-) x AIM(-/-) mice only. AIM have some regulatory roles in inflammation and progression of dysplasia to carcinoma in TCRalpha(-/-) mice.