Up-Regulation of TLR7-Mediated IFN-α Production by Plasmacytoid Dendritic Cells in Patients With Systemic Lupus Erythematosus

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ID: 104432
2018
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Ranked #33 of 111 articles by views in Frontiers in immunology

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Abstract
Objectives: Aberrant and persistent production of interferon-α (IFN-α) by plasmacytoid dendritic cells (pDCs) is known to play a key role in the pathogenesis of systemic lupus erythematosus (SLE). To assess the precise function of pDCs in SLE patients, we investigated the differential regulation of Toll-like receptor 7 (TLR7) and TLR9 responses during IFN-α production by pDCs.Methods: Peripheral blood mononuclear cells (PBMCs) in SLE patients without hydroxychloroquine treatment, rheumatoid arthritis patients and heathy controls were stimulated with TLR7 and TLR9 agonists. To investigate the priming effect by cytokines, PBMCs from healthy controls were pre-treated with various cytokines and stimulated with TLR7 and TLR9 agonists. The IFN-α production in pDCs was detected by flow cytometry.Results: TLR7-mediated IFN-α production was up-regulated and correlated positively with disease activity in SLE. Conversely, TLR9-mediated IFN-α production was down-regulated. Differential regulation of TLR7/9 response in SLE was independent of TLR7 and TLR9 expression levels. Furthermore, in vitro experiments indicated that TLR7-mediated IFN-α production was up-regulated by pre-treatment with type I IFN, whereas TLR9-mediated IFN-α production was down-regulated by pre-treatment with type II IFN.Conclusions: Our study indicates the association between up-regulation of TLR7- mediated IFN-α production by pDCs and disease activity and that TLR7 and TLR9 responses were reversely regulated on pDCs in SLE patients. Thus, type I IFN and TLR7-mediated IFN-α production were involved in a vicious cycle, causing hyper production of IFN-α by pDCs during the pathogenic processes of SLE.
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sakata2018upregulationfrontiers Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Sakata, Kei;Sakata, Kei;Nakayamada, Shingo;Miyazaki, Yusuke;Kubo, Satoshi;Ishii, Akina;Ishii, Akina;Nakano, Kazuhisa;Tanaka, Yoshiya;
Journal Frontiers in immunology
Year 2018
DOI
DOI not found
URL
https://www.frontiersin.org/article/10.3389/fimmu.2018.01957/full
Keywords
Medicine (General) Medicine Pediatrics Diseases of the circulatory (Cardiovascular) system Immunologic diseases. Allergy general works internal medicine diseases of the musculoskeletal system systemic lupus erythematosus toll-like receptor 7 allergy

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