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LPS activation is required for migratory activity and antigen presentation by tolerogenic dendritic cells.

Anderson, Amy E, Swan, David, Sayers, Bethan L, Harry, Rachel A, Patterson, Angela M, von Delwig, Alexei, Robinson, John H, Isaacs, John D and Hilkens, Catharien M U (2008) LPS activation is required for migratory activity and antigen presentation by tolerogenic dendritic cells. Journal of leukocyte biology, 85 (2). pp. 243-50. ISSN 0741-5400

Item Type: Article

Abstract

Autoimmune pathologies are caused by a breakdown in self-tolerance. Tolerogenic dendritic cells (tolDC) are a promising immunotherapeutic tool for restoring self-tolerance in an antigen-specific manner. Studies about tolDC have focused largely on generating stable maturation-resistant DC, but few have fully addressed questions about the antigen-presenting and migratory capacities of these cells, prerequisites for successful immunotherapy. Here, we investigated whether human tolDC, generated with dexamethasone and the active form of vitamin D3, maintained their tolerogenic function upon activation with LPS (LPS-tolDC), while acquiring the ability to present exogenous autoantigen and to migrate in response to the CCR7 ligand CCL19. LPS activation led to important changes in the tolDC phenotype and function. LPS-tolDC, but not tolDC, expressed the chemokine receptor CCR7 and migrated in response to CCL19. Furthermore, LPS-tolDC were superior to tolDC in their ability to present type II collagen, a candidate autoantigen in rheumatoid arthritis. tolDC and LPS-tolDC had low stimulatory capacity for allogeneic, naïve T cells and skewed T cell polarization toward an anti-inflammatory phenotype, although LPS-tolDC induced significantly higher levels of IL-10 production by T cells. Our finding that LPS activation is essential for inducing migratory and antigen-presenting activity in tolDC is important for optimizing their therapeutic potential.

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More Information

Depositing User: David Swan

Identifiers

Item ID: 16675
Identification Number: https://doi.org/10.1189/jlb.0608374
ISSN: 0741-5400
URI: http://sure.sunderland.ac.uk/id/eprint/16675
Official URL: https://academic.oup.com/jleukbio/article/85/2/243...

Users with ORCIDS

ORCID for David Swan: ORCID iD orcid.org/0000-0002-6480-9621

Catalogue record

Date Deposited: 10 Oct 2023 12:19
Last Modified: 24 Apr 2024 12:48

Contributors

Author: David Swan ORCID iD
Author: Amy E Anderson
Author: Bethan L Sayers
Author: Rachel A Harry
Author: Angela M Patterson
Author: Alexei von Delwig
Author: John H Robinson
Author: John D Isaacs
Author: Catharien M U Hilkens

Subjects

Sciences > Biomedical Sciences

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