The opposing roles of IL-21 and TGFβ1 in chronic inflammatory bowel disease

There are large numbers of T-cells in the mucosa of the intestine in healthy individuals. The stimulus for their presence is the normal gut microbiota. For unknown reasons, in patients with IBD (inflammatory bowel disease), there is inappropriate and chronic activation of mucosal T-cells which leads to gut damage and severe morbidity. In one form of IBD, namely Crohn's disease, the T-cells are probably responding to the microbiota. T-cell survival in the gut wall is dependent on pro-inflammatory cytokines and antibody-mediated inhibition of one of these cytokines, TNF alpha (tumour necrosis factor alpha), has shown efficacy in patients, thus encouraging investigations of other ways to control mucosal T-cell responses. In the present paper, we give a brief review of T-cell immunology in IBD and then discuss how two particular cytokines, namely IL-21 (interleukin 21), which is generally pro-inflammatory and important in gut T-cell survival and in maintaining Th17 cells, and TG beta 1 (transforming growth factor beta 1), which is generally immunosuppressive, play opposing roles in gut inflammation.