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Immune-trafficking in celiac disease: mast cell the traffic cop?

Published Online: September 9, 2016

Celiac disease (CD) is a gluten-sensitive enteropathy that develops in genetically susceptible individuals by exposure to cereal gluten proteins. CD is considered mainly a T cell–mediated immune disorder in which CD4+ T cells, preferentially, recognize deaminated gluten peptides in the context of major histocompatibility class II molecules and play a central role in the development of the disease. However, increasing evidence supports the role of innate immunity in the development of CD.

In a recent study published in The Journal of Allery & Clinical Immunology (JACI) Frossi and colleagues have investigated and characterized the types and the interplay of immune cells present in the duodenal mucosa as a consequence of both adaptive and innate immune responses to undigested gliadin peptides. The researchers analyzed and scored intestinal biopsies of CD patients, according to the Marsh classification, and studied the immune cell subsets, and found that histological damage progression was associated with the density of infiltrating MCs (mast cells). Additionally, histological analysis together with in vitro and ex vivo data indicate that the inflammatory MC phenotype skews myeloid populations towards a Th-1 polarizing environment along the stages of the disease. They demonstrated that in vitro human mast cell lines and mouse bone marrow-derived mast cells can bind the non-immunogenic gliadin peptide p31-43, be activated via Myd88 pathways and release inflammatory cytokines.

Frossi’s paper unveils a new role of MCs in shaping the inflammatory microenvironment of gluten- induced enteropathy in the onset and development of the disease. Additionally, the paper suggests that intestinal MCs are trained to be more prone to an inflammatory response after gliadin challenge. This could help to explain the fast relapse of the disease or unpleasant reactions in CD patients despite what is the T cell contribution to the disease. The authors’ finding suggest that a modulation of the MCs activation could be possible new therapeutic approach to CD or inflammatory diseases of the gut.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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