Toll-like receptors-mediated pathways activate inflammatory responses in the esophageal mucosa of adult eosinophilic esophagitis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-04

AUTHORS

Ángel Arias, María Vicario, David Bernardo, José M. Olalla, Marina Fortea, Ana Montalban-Arques, Pilar Martínez-Fernández, Ana M. González-Castro, Teresa Mota-Huertas, Laura Arias-González, Alfredo J. Lucendo

ABSTRACT

OBJECTIVES: Esophageal microbiota and regulation of adaptive immunity are increasingly being investigated in eosinophilic esophagitis (EoE). Toll-like receptors (TLRs) play a central role in the initiation and maintenance of innate immune activity. Our objective was to characterize the esophageal and duodenal innate immune response in EoE and its modulation by dietary therapy. METHODS: Esophageal and duodenal biopsy samples were collected from 10 adults with untreated EoE, before and after effective treatment with a six-food elimination diet (SFED), and 10 controls with normal esophagus. In all cases, bacterial load (by mRNA expression of 16S), TLRs, mucins, transcription factors, interleukins, components of the NKG2D system, and innate immunity effectors were assessed by qPCR. Protein expression of TLRs were also determined by immunofluorescence. RESULTS: Bacterial load and TLR1, TLR2, TLR4, and TLR9 were overexpressed on biopsies with active EoE compared with controls. Muc1 and Muc5B genes were downregulated while Muc4 was overexpressed. Upregulation of MyD88 and NFκB was found together with IL-1β, IL-6, IL-8, and IL-10 mediators and PER-1, iNOS, and GRZA effectors. NG-K2D components (KLRK1, IL-15, MICB) were also upregulated. In all cases, changes in active EoE were normalized following SFED and mucosal healing. Duodenal samples also showed increased expressions of TLR-1, TLR-2, and TLR-4, but not 16S or any other mediators nor effectors of inflammation. CONCLUSIONS: Esophageal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease. More... »

PAGES

147

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41424-018-0017-4

DOI

http://dx.doi.org/10.1038/s41424-018-0017-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103607393

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29691386


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429 schema:name Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
430 Laboratory of Translational Mucosal Immunology, Digestive Diseases Research Unit, Vall d’Hebron Institut de Recerca, Department of Gastroenterology, Hospital Universitari Vall d´Hebron, Barcelona, Spain
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432 https://www.grid.ac/institutes/grid.411251.2 schema:alternateName Hospital Universitario de La Princesa
433 schema:name Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
434 Gut Immunology Research Group, Hospital Universitario de La Princesa e Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
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436 https://www.grid.ac/institutes/grid.413448.e schema:alternateName Instituto de Salud Carlos III
437 schema:name Centro de Investigación Biomédica en Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain
438 Institute of Medical and Molecular Genetics (INGEMM), Idipaz Research Laboratory, Hospital Universitario La Paz, Madrid, Spain
439 rdf:type schema:Organization
440 https://www.grid.ac/institutes/grid.452371.6 schema:alternateName Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
441 schema:name Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
442 Research Unit, Hospital General La Mancha Centro, Alcázar de San Juan, Ciudad. Real, Spain
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444 https://www.grid.ac/institutes/grid.470217.7 schema:alternateName Hospital General de Tomelloso
445 schema:name Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
446 Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain
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