Protective Effects of Aryl Hydrocarbon Receptor Signaling in Celiac Disease Mucosa and in Poly I:C-Induced Small Intestinal Atrophy Mouse Model.

Front Immunol 2019 4;10:91. Epub 2019 Feb 4.

Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy.

Aryl hydrocarbon receptor (AhR), a transcription factor activated by a large number of natural and synthetic agents, modulates the activity of immune cells in the gut and represents an important link between the environment and immune-mediated pathologies. In this study, we investigated the role of AhR in celiac disease (CD), a gluten-driven enteropathy. AhR expression was evaluated in intestinal biopsies taken from patients with CD and controls by real-time polymerase chain reaction (PCR), immunohistochemistry and flow cytometry. AhR was also analyzed in organ cultures of duodenal biopsies taken from inactive CD patients incubated in presence or absence of peptic-tryptic digest of gliadin. IFN-γ, TNF-α, granzyme B, and perforin expression was evaluated in anti-CD3/CD28-activated intestinal lamina propria mononuclear cells (LPMC) and intestinal intra-epithelial cells (IEL) of active CD patients cultured in the presence or absence of the AhR agonist 6-formylindolo(3, 2-b)carbazole (Ficz). Finally, the protective role of AhR was evaluated in a mouse model of poly I:C-driven small intestine damage. AhR RNA transcripts were reduced in active CD samples as compared to inactive CD and normal controls. Flow cytometry confirmed such results and showed a reduction of AhR in both IEL and LPMC of active CD patients. The addition of a peptic-tryptic digest of gliadin to organ cultures of duodenal biopsies taken from inactive CD patients reduced AhR expression. Treatment of CD IEL and LPMC with Ficz reduced the levels of inflammatory cytokines, granzyme B and perforin. Mice injected with Ficz were protected against poly I:C-induced intestinal lesions. Our findings suggest that defective AhR-driven signals could contribute to amplify pathogenic responses in the gut of CD patients.

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2019.00091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369162PMC
December 2019
2 Reads

Publication Analysis

Top Keywords

ahr
9
flow cytometry
8
organ cultures
8
expression evaluated
8
iel lpmc
8
mouse model
8
cultures duodenal
8
role ahr
8
duodenal biopsies
8
digest gliadin
8
granzyme perforin
8
active patients
8
peptic-tryptic digest
8
presence absence
8
biopsies inactive
8
inactive patients
8
poly ic-induced
8
ahr expression
8
aryl hydrocarbon
8
celiac disease
8

Similar Publications