Crohn's disease is facilitated by a disturbance of programmed death-1 ligand 2 on blood dendritic cells

Clinical & Translational Immunology
Rebecca FaleiroMichelle Wykes

Abstract

Crohn's disease (CD) is characterised by inflammation, predominantly associated with ilea. To investigate the basis for this inflammation in patients with CD, we examined dendritic cells (DC) which are pivotal for maintenance of immunological tolerance in the gut. Ileal biopsies and blood DCs from CD patients and controls were examined by microscopy and flow cytometry for PD-L1 and PD-L2 expression, as PD-L1 has been implicated in colitis but the contribution of PD-L2 is less clear. In vitro studies, of blood samples from CD patients, were used to demonstrate a functional role for PD-L2 in disease pathogenesis. Quantitative microscopy of CD11c+ DCs in inflamed and noninflamed ilea from CD patient showed > 75% loss of these cells from the villi, lamina propria and Peyer's patches compared with non-CD controls. Given this loss of DCs from ilia of CD patients, we hypothesised DCs may have migrated to the blood as these patients can have extra-intestinal symptoms. We thus examined blood DCs from CD patients by flow cytometry and found significant increases in PD-L1 and PD-L2 expression compared with control samples. Microscopy revealed an aggregated form of PD-L2 expression, known to drive Th1 immunity, in CD patients but not in co...Continue Reading

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Citations

Dec 5, 2020·International Journal of Molecular Sciences·Marina ChulkinaIrina V Pinchuk
Mar 20, 2021·Stem Cell Research & Therapy·Alexander MarkovAli Hassanzadeh
Aug 8, 2021·International Journal of Molecular Sciences·Shaghayegh Baradaran GhavamiMohammad Reza Zali

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Methods Mentioned

BETA
biopsies
biopsy
flow cytometry
confocal microscopy
FACS
FCS

Software Mentioned

FCS express
FSC express
BD FACSDiva
De Novo
Zen
GraphPad Prism
Vectra
FACSDiva
LEGENDplex
BD

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