Gliadin peptides as triggers of the proliferative and stress/innate immune response of the celiac small intestinal mucosa.
Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides (i.e., peptide 31-43, P31-43) is the cytokine interleukin-15 (IL-15). The role of epithelial growth factor (EGF) as a mediator of enterocyte proliferation and the innate immune response has been described. In this paper, we review the most recent literature on the mechanisms responsible for triggering the up-regulation of these mediators in CD by gliadin peptides. We will discuss the role of P31-43 in enterocyte proliferation, structural changes and the innate immune response in CD mucosa in cooperation with EGF and IL-15, and the mechanism of up-regulation of these mediators related to vesicular trafficking. We will also review the literature that focuses on constitutive alterations of the structure, signalling/proliferation and stress/innate immunity pathways of CD cells. Finally, we will discuss how these pathways can be triggered by gliadin peptide P31-43 in controls, mimicking the celiac cellular phenotype.
Department of Translational Medical Science (Section of Pediatrics), University of Naples Federico II, Via S. Pansini 5, Naples 80131, Italy. mv.barone@unina.it.
Maria Vittoria
MV
Barone
Department of Translational Medical Science (Section of Pediatrics), University of Naples Federico II, Via S. Pansini 5, Naples 80131, Italy. salauric@unina.it.
Riccardo
R
Troncone
European Laboratory for the Investigation of Food Induced Diseases (ELFID), University of Naples Federico II, Via S. Pansini 5, Naples 80131, Italy. salauric@unina.it.
Salvatore
S
Auricchio
D000818:Animals; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D020895:Enterocytes / Q000276:immunology / Q000473:pathology; D004815:Epidermal Growth Factor / Q000276:immunology; D066246:ErbB Receptors / Q000276:immunology; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D019409:Interleukin-15 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*
D019409:Interleukin-15; D010446:Peptide Fragments; C549457:gliadin p31-43; D004815:Epidermal Growth Factor; D005903:Gliadin; D066246:ErbB Receptors