|Chronic inflammatory diseases of the intestine impose significant healthcare, social and economic problems throughout Europe. A multifactorial aetiology with environmental, immulogical and genetic components is suggested. The proposal will use three mouse models of intestinal inflammation to examine the interactions between the intestinal bacterial micro flora and the mucosal immune system. The effects of individual bacterial species and their defined antigens on induction and regulation of pathogenesis will be investigated in selectively re- colonised germfree systems. The role of the intestinal epithelium and associated extra cellular matrix components will be explored. New model systems to analyse the involvement of specific gene transcription factors in the initiation and control of mucosal inflammation will be produced.