title: New insights into the cellular immunology of the intestine in relation to the pathophysiology of inflammatory bowel diseases.
abstract: 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.
authors.affiliation: Department of Clinical Biology-Immunohaematology Unit, University Hospital St. Luc, Université catholique de Louvain,Brussels. latinne@imex.ucl.ac.be
authors.forename: Dominique
authors.initials: D
authors.lastname: Latinne
authors.forename: René
authors.initials: R
authors.lastname: Fiasse
mesh_terms: D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D018928:Immunity, Mucosal / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000503:physiopathology; D007422:Intestines / Q000276:immunology*