New insights into the cellular immunology of the intestine in relation to the pathophysiology of inflammatory bowel diseases

The authors review advances about altered immunological cel- lular mechanisms in inflammatory bowel diseases (IBD). The innate immune response might play a role in the inductive phase : epithelial barrier defect, production of inflammatory cytokines and defective neutrophil function. Dendritic cells have a pivotal role, since they sense the nature of the micro-organisms in the intestine in order to drive either adaptive immune responses through IL-12 or IL-4 and co-stimulatory molecules, or immuno- tolerance through regulatory T cells (Tr). T helper(Th)1 cytokines (IFNg, TNF-a, IL-12) are secreted in excess in Crohn's disease (CD) whereas in ulcerative colitis an atypical Th2 immune response (IL-4, TGFb) has been reported. However, activation of Th can only lead to effective immune response if co-stimulatory molecules expressed on activated T cells bind to their specific lig- ands on the antigen-presenting-cells, mesenchymal and endothe- lial cells. This binding is necessary to generate an effective immune response, to enhance expression of adhesion molecules and T cell recruitment, promoting chronic inflammation in IBD. A defective function of Tr might contribute to excessive T cell response. Innate CD4 + CD25 + Tr derived from the thymus represent 5-10% of T cells in peripheral lymphoid organs. Acquired peripheral Tr downregulate the immune response through IL-10 and TGF-b production. In IBD effector T cells might downregulate the devel- opment of Tr cells in the thymus. Another defective mechanism in CD is T cell resistance to apoptosis, leading to inappropriate immune homeostasis and accumulation of T cells in the tissues. New therapeutic agents have been proposed for correcting defi- ciencies of innate immunity or reducing excessive immune responses, with promising results confirmed by randomized con- trolled trials. (Acta gastroenterol. belg., 2006, 69, 393-405).