Constitutive alterations in vesicular trafficking increase the sensitivity of cells from celiac disease patients to gliadin.
PMID 31123714 · Communications biology · 2019 · DOI 10.1038/s42003-019-0443-1
Authors: Giuliana Lania; Merlin Nanayakkara; Mariantonia Maglio; Renata Auricchio; Monia Porpora; Mariangela Conte; Maria Antonietta De Matteis; Riccardo Rizzo; Alberto Luini; Valentina Discepolo; Riccardo Troncone; Salvatore Auricchio; Maria Vittoria Barone
Abstract
Celiac Disease (CD) is an autoimmune disease characterized by inflammation of the intestinal mucosa due to an immune response to wheat gliadins. Some gliadin peptides (e.g., A-gliadin P57-68) induce an adaptive Th1 pro-inflammatory response. Other gliadin peptides (e.g., A-gliadin P31-43) induce a stress/innate immune response involving interleukin 15 (IL15) and interferon α (IFN-α). In the present study, we describe a stressed/inflamed celiac cellular phenotype in enterocytes and fibroblasts probably due to an alteration in the early-recycling endosomal system. Celiac cells are more sensitive to the gliadin peptide P31-43 and IL15 than controls. This phenotype is reproduced in control cells by inducing a delay in early vesicular trafficking. This constitutive lesion might mediate the stress/innate immune response to gliadin, which can be one of the triggers of the gliadin-specific T-cell response.
Adolescent; Case-Control Studies; Celiac Disease; Child; Child, Preschool; Endocytosis; Endosomes; Enterocytes; ErbB Receptors; Fibroblasts; Gliadin; Humans; Immunity, Innate; Interleukin-15; Intestinal Mucosa; Peptide Fragments; Th1 Cells
Cite
Giuliana Lania; Merlin Nanayakkara; Mariantonia Maglio; Renata Auricchio; Monia Porpora; Mariangela Conte; Maria Antonietta De Matteis; Riccardo Rizzo; Alberto Luini; Valentina Discepolo; Riccardo Troncone; Salvatore Auricchio; Maria Vittoria Barone. Constitutive alterations in vesicular trafficking increase the sensitivity of cells from celiac disease patients to gliadin. Communications biology (2019). PMID 31123714. DOI 10.1038/s42003-019-0443-1.