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Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota-Key players in the pathogenesis of celiac disease

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World Journal of Gastroenterology 2017年第42期23卷 7505-7518页

作者： Bozena Cukrowska Agnieszka Sowińska Joanna Beata Bierla elzbieta czarnowska Anna Rybak Urszula Grzybowska-Chlebowczyk Department of Pathology The Children's Memorial Health Institute Department of Gastroenterology Division of Neurogastroenterology and MotilityGreat Ormond Street Hospital Department of Pediatrics School of MedicineMedical University of Silesia

Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens(HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive(specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiotahomeostasis, epithelial layer integrity, and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.

关键词： Celiac disease Intestinal microbiota Epithelium Intraepithelial lymphocytes Intestinal barrier

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Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

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Cellular & Molecular Immunology 2016年第2期13卷 251-262页

作者： Hana Kozakova Martin Schwarzer Ludmila Tuckova Dagmar Srutkova elzbieta czarnowska Ilona Rosiak Tomas Hudcovic Irma Schabussova Petra Hermanova Zuzana Zakostelska Tamara Aleksandrzak-Piekarczyk Anna Koryszewska-Baginska Helena Tlaskalova-Hogenova Bozena Cukrowska Laboratory of Gnotobiology Institute of Microbiology Academy of Sciences of the Czech Republic Novy Hradek Czech Republic Department of Pathology the Children's Memorial Health Institute Warsaw Poland Institute of Specific Prophylaxis and Tropical Medicine Medical University of Vienna Vienna Austria Institute of Biochemistry and Biophysics Polish Academy of Sciences Warsaw Poland

Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v I using a gnotobiotic mouse model. We showed that Lactobacillus （L.） rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 （TLR2） and nucleotide-binding oligomerization domain-containing protein 2 （NOD2） receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free （GF） mice with a mixture of all three strains （Lmix） improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v I allergen showed significantly lower levels of allergen-specific IgE, IgG 1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor （TGF）-β level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-β after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-β. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans,

关键词： allergic sensitization germ-free intestinal barrier Lactobacillus probiotics

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