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Le système immunitaire muqueux dans les maladies inflammatoires intestinales

The mucosal immune system in inflammatory bowel disease

El sistema inmunitario mucoso en las enformedades inflamatorias intestinales

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Acta Endoscopica

Résumé

Ľimmunité sécrétaire est la partie la mieux définie du système immunitaire muqueux. Ce mécanisme de défense humorale adapté dépend ďune coopération étroite entre ľépithélium sécrétoire et les plasmocytes locaux. Ces immunocytes produisent de préférence des diméres et de plus larges polyméres ďIgA. Les IgA polymériques (poly-IgA) et les pentaméres IgM, contiennent des chaînes J et peuvent pour cette raison, être liés au composant sécrétoire épithélial (CS). Son fonctionnement en tant que récepteur de transport poly-Ig est nécessaire à la production ďIgA sécrétoire (SIgA) et ďIgM sécrétoire (SIgM). Des faits multiples montrent que les anticorps SIgA et SIgM assurent ľexclusion immunitaire, ’opposant ainsi à la colonisation microbienne de la muqueuse et à la pénétration ďantigènes solubles. La production muqueuse de poly-IgA est déréglée de façon significative dans les maladies inflammatoires intestinales (Mil), ce dont témoigne la réduction drastique de ľexpression chaîne-J au niveau des immunocytes IgA muqueux. En outre, on observe une déviation significative des sous-classes IgA2 vers les IgAl, moins résistantes à la dégradation protéolytique. Ces modifications, associées à une activation des lymphocytes T et des macrophages, et à une augmentation importante des cellules productrices ďIgG, altèrent ľhoméostase immunitaire locale et menacent la défense muqueuse. Bien qu’un accroissement de la totalité de la population immunocytaire muqueuse puisse compenser la production relativement réduite de poly-IgA, la diminution de ľexpression CS au niveau de ľépithélium régénératif ou dysplasique, montre que le système SIgA n’est en aucun cas intact dans les Mil. Ľactivation du complément observée en relation avec des dépôts d'IgGl épithéliaux chez les patients atteints de recto-colite ulcéreuse, suggère que ľépithélium de surface est soumis à une agression immunitaire. Ces dépôts épithéliaux contiennent réguliérement des complexes terminaux du complément (CTC) et trés souvent du C3b, témoins ďune activation persistante. La comparaison entre des jumeaux univitellins mais différents du point de vue colite ulcéreuse, suggère qu’une réponse IgGl locale prononcée pourrait, en partie, être génétiquement déterminée ; une possibilité intéressante serait que ce phénomène représente une réponse autoimmune (anti-épithéliale). Néanmoins, ľévénement initial, déclenchant le mécanisme immunopathologique des MII demeure inconnu. La suppression de la tolérance orale aux antigènes endoluminaux a été suggérée comme un mécanisme ďautoentretien possible, probablement par interaction entre les lymphocytes T CD4b+ activés et les cellules épithéliales avec une expression HLA classe II exagérément intense.

Summary

Secretory immunity is the best defined part of the mucosal immune system. This adaptive humoral defence mechanism depends on a fascinating cooperation between the secretory epithelium and the local plasma cells. These immunocytes produce preferentially dimers and larger polymers of IgA. Such polymeric IgA (poly-IgA), and also pentameric IgM, contain J chain and can therefore become bound to the epithelial secretory component (SC). Its function as a poly-Ig transport receptor is necessary for the generation of secretory IgA (SIgA) and secretory IgM (SIgM). There is abundant evidence that SIgA and SIgM antibodies perform immune exclusion, thereby counteracting microbial colonization and mucosal penetration of soluble antigens. The mucosal poly-IgA production is significantly down-regulated in inflammatory bowel disease (IBD), as revealed by a strikingly decreased J-chain expression in mucosal IgA immunocytes. There is moreover a significant shift from the IgA2 to the IgAl subclass, which is less resistant to proteolytic degradation. These changes, along with activation of T cells and macrophages and a dramatic increase of IgG-producing cells, will alter the local immunological homeostasis and jeopardize mucosal defence. Although the overall increase of the total mucosal immuno- cyte population may compensate for the relatively reduced poly-IgA production, decreased SC expression in regenerat- ing and dysplastic epithelium shows that the SIgA system is by no means intact in IBD. Complement activation observed in relation to epithelial IgGl deposits in

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Authors and Affiliations

  1. Laboratory for Immunohistochemistry and Immunopathology LIIPAT, Norway

    P. Brandtzaeg, T. S. Halstensen & K. Kett

  2. Institute of Pathology, University of Oslo, The National Hospital, Rikshospitalet, Oslo, Norway

    P. Brandtzaeg, T. S. Halstensen & K. Kett

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  1. P. Brandtzaeg
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Brandtzaeg, P., Halstensen, T.S. & Kett, K. Le système immunitaire muqueux dans les maladies inflammatoires intestinales. Acta Endosc 21, 219–231 (1991). https://doi.org/10.1007/BF02968710

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