Lost therapeutic potential of monocyte-derived dendritic cells through lost tissue homing: stable restoration of gut specificity with retinoic acid

Authors

  • D. Bernardo,

    1. Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
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  • E. R. Mann,

    1. Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
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  • H. O. Al-Hassi,

    1. Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
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  • N. R. English,

    1. Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
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  • R. Man,

    1. Department of Gastroenterology, St Mark's Hospital, North West London Hospitals NHS Trust, Harrow, UK
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  • G. H. Lee,

    1. Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
    2. Department of Gastroenterology, St Mark's Hospital, North West London Hospitals NHS Trust, Harrow, UK
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  • E. Ronde,

    1. Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
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  • J. Landy,

    1. Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
    2. Department of Gastroenterology, St Mark's Hospital, North West London Hospitals NHS Trust, Harrow, UK
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  • S. T. C. Peake,

    1. Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
    2. Department of Gastroenterology, St Mark's Hospital, North West London Hospitals NHS Trust, Harrow, UK
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  • A. L. Hart,

    1. Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
    2. Department of Gastroenterology, St Mark's Hospital, North West London Hospitals NHS Trust, Harrow, UK
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  • S. C. Knight

    Corresponding author
    • Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, UK
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Correspondence: S. C. Knight, Antigen Presentation Research Group, Imperial College London, Northwick Park and St Mark's Campus, Level 7W St Mark's Hospital, Watford Road, Harrow HA1 3UJ, UK.

E-mail: s.knight@imperial.ac.uk

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.

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