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 cellular 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 immunotolerance through regulatory T cells (Tr). T helper(Th)1 cytokines (IFNgamma, TNF-alpha, IL-12) are secreted in excess in Crohn's disease (CD) whereas in ulcerative colitis an atypical Th2 immune response (IL-4, TGFbeta) 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 ligands 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-beta production. In IBD effector T cells might downregulate the development 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 deficiencies of innate immunity or reducing excessive immune responses, with promising results confirmed by randomized controlled trials.
Latinne
Dominique
D
Department of Clinical Biology-Immunohaematology Unit, University Hospital St. Luc, Université catholique de Louvain,Brussels. latinne@imex.ucl.ac.be
Fiasse
René
R
D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D018928:Immunity, Mucosal / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000503:physiopathology; D007422:Intestines / Q000276:immunology*