Volume 69 - 2006 - Fasc.4 - Symposium
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).
Apoptosis as a therapeutic paradigm in inflammatory bowel diseases
Evidence is increasing that a defect in apoptosis is involved in the pathogenesis of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). CD seems to be the cause of an intrinsic defect in the apoptotic pathway of (autore- active) T cells, resulting in excessive T cell responses. In UC, an increased rate of apoptosis of epithelial cells is observed. In this review we will describe apoptotic mechanisms and their associa- tion to IBD. In addition, we will review how specific therapeutic approaches interact at different levels with the apoptotic pathway. (Acta gastroenterol. belg., 2006, 69, 406-412).
Intestinal helminths : a clue explaining the low incidence of inflammatory bowel diseases in Subsaharan Africa ? Potential benefits and hazards of helminth therapy
In their review, the authors state that the very low incidence and prevalence of IBD in sub-Saharan Africa cannot be explained by genetic factors since in Black populations of the USA and UK, the incidence of these diseases is approaching that of the white popu- lations.
Beside helminths whose intestinal infestation is frequent in sub- Saharan Africa, other micro-organisms such as atypical mycobac- teria, lactobacilli, etc, might have been reduced in Western popu- lation. This is a new variant of the Hygiene hypothesis. After Rook et al., these micro-organisms were acting as adjuvants for induc- tion of T regulatory cells which, associated with antigen-present- ing cells secrete IL-10 and TGF-b, inhibiting the maturation of CD4 T cells to Th1 and Th2 effector cells, and consequently reduc- ing the occurrence of Th1-mediated diseases like Crohn's disease and Th2-mediated diseases like ulcerative colitis.
The effects of intestinal helminths on host immunity have been studied in Ethiopian Jews emigrated to Israël. Thorough studies before and after deworming have demonstrated that chronic helminth infestation provokes a state of chronic immune activa- tion with anergy, reversible after deworming.
Administration of ova of Trichuris suis, an helminth non patho- genic in man, has given encouraging results in the treatment o Crohn's disease and ulcerative colitis with a good safety record but long-term trials are needed since the potentially harmful effects of helminths on immunity. (Acta gastroenterol. belg., 2006, 69, 418- 422).
