期刊
IMMUNOLOGY
卷 139, 期 2, 页码 219-226出版社
WILEY-BLACKWELL
DOI: 10.1111/imm.12073
关键词
CD4(+) T cell; dendritic cell; dexamethasone; protease-activated receptor-2; tissue factor
类别
资金
- NKRF (KRUK) Clinical Fellowship
- Medical Research Council, UK [G0401591, G0801965]
- Garfield Weston Foundation
- British Heart Foundation
- Guy's and St Thomas' Charity
- GSTT Kidney Patients Association
- National Institute for Health Research (NIHR) Biomedical Research Centre
- King's College London
- Medical Research Council [G0801965, G0401591, MR/J006742/1] Funding Source: researchfish
- MRC [G0401591, G0801965] Funding Source: UKRI
The precise function of tissue factor (TF) expressed by dendritic cells (DC) is uncertain. As well as initiating thrombin generation it can signal through protease-activated receptor 2 (PAR-2) when complexed with factor VIIa. We investigated the expression and function of TF on mouse bone marrow (BM) -derived DC; 20% of BM-derived DC expressed TF, which did not vary after incubation with lipopolysaccharide (LPS) or dexamethasone (DEX). However, the pro-coagulant activity of DEX-treated DC in recalcified plasma was 30-fold less than LPS-treated DC. In antigen-specific and allogeneic T-cell culture experiments, the TF on DEX-treated DC provided a signal through PAR-2, which contributed to the reduced ability of these cells to stimulate CD4+ T-cell proliferation and cytokine production. In vivo, an inhibitory anti-TF antibody and a PAR-2 antagonist enhanced antigen-specific priming in two models where antigen was given without adjuvant, with an effect approximately 50% that seen with LPS, suggesting that a similar mechanism was operational physiologically. These data suggest a novel TF and PAR-2-dependent mechanism on DEX-DC in vitro and unprimed DC in vivo that contributes to the low immunogenicity of these cells. Targeting this pathway has the potential to influence antigen-specific CD4+ T-cell activation.
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