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Lost therapeutic potential of monocyte-derived dendritic cells through lost tissue homing: Stable restoration of gut specificity with retinoic acid
Bernardo, D Mann, ER Al-Hassi, Hafid Omar English, NR Man, R Lee, GH Ronde, E Landy, J Peake, STC Hart, AL
Bernardo, D
Mann, ER
Al-Hassi, Hafid Omar
English, NR
Man, R
Lee, GH
Ronde, E
Landy, J
Peake, STC
Hart, AL
Editors
Other contributors
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Epub Date
Issue Date
2013-09-08
Submitted date
Alternative
Abstract
Summary: Human monocyte-derived dendritic cells (DC) (MoDC) are utilized for immunotherapy. However, in-vitro immunological effects are often not mirrored in vivo. We studied the tissue-homing potential of MoDC. Circulating monocytes and DC expressed different tissue-homing markers and, during in-vitro development of MoDC, homing marker expression was lost resulting in a 'homeless' phenotype. Retinoic acid (RA) induced gut-homing markers (β7 and CCR9) and a regulatory phenotype and function [decreased human leucocyte antigen D-related (HLA-DR) and increased ILT3 and fluorescein isothiocyanate (FITC-dextran uptake) in MoDC]. RA-MoDC were less stimulatory and primed conditioned T cells with a gut-homing profile (β7+CLA-). Unlike the normal intestinal microenvironment, that from inflamed colon of ulcerative colitis (UC) patients did not induce regulatory properties in MoDC. However, RA-MoDC maintained their regulatory gut-specific properties even in the presence of UC microenvironment. Therefore, MoDC may be ineffectual for immunotherapy because they lack tissue-homing and tissue-imprinting specificity. However, MoDC rehabilitation with gut-homing potential by RA could be useful in promoting immunotherapy in pathologies such as UC. © 2013 The Authors. Clinical and Experimental Immunology published by John Wiley & Sons Ltd on behalf of British. Society for Immunology.
Citation
Bernardo, D., Mann, E.R., Al-Hassi, H.O. et al (2013) Lost therapeutic potential of monocyte-derived dendritic cells through lost tissue homing: Stable restoration of gut specificity with retinoic acid, Clinical and Experimental Immunology, 174(1), pp. 109-119.
Publisher
Research Unit
PubMed ID
23607934 (pubmed)
PubMed Central ID
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Type
Journal article
Language
en
Description
© 2013 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/cei.12118
Series/Report no.
ISSN
0009-9104
EISSN
1365-2249
ISBN
ISMN
Gov't Doc #
Sponsors
This work was supported by Marie Curie Intra European Fellowship (FP7‐people‐IEF‐2008‐235993), St Mark's Hospital Foundation the Brigid Balfour Fund and the BBSRC (WMNI P33458).