Article Text

PDF

105 Toll-like receptor 7-, but not toll-like receptor 9-, mediated interferon-Α production from plasmacytoid dendritic cells in patients with systemic lupus erythematosus
  1. K Sakata,
  2. S Nakayamada,
  3. Y Miyazaki,
  4. S Kubo,
  5. K Nakano and
  6. Y Tanaka
  1. University of Occupational and Environmental Health, The First Department of Internal Medicine, Kitakyushu, Japan

Abstract

Background and aims Aberrant and persistent production of type I interferon (IFN) is known to play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE), and plasmacytoid dendritic cells (pDCs) are the major source of type I IFN upon toll-like receptor 7 (TLR7) and TLR9 stimulation. However the respective impacts of TLR7 and TLR9 responses on type I IFN production in SLE has not been addressed.To investigate the precise function of pDCs in SLE patients, we shed light upon the differential regulation of TLR7/9 responses during type I IFN production from pDCs.

Methods PBMCs from SLE patients and healthy controls were analysed in the presence of a TLR7 agonist loxoribine and a TLR9 agonist CpG2216. The IFN-α production in Lin-HLA-DR+CD123+CD11c- pDCs was detected by flow cytometry.

Results We demonstrated that TLR7-mediated IFN-α production were up-regulated and were positively correlated with disease activity, conversely, TLR9-mediated IFN-α production were down-regulated in SLE. The differential regulation of TLR7/9 responses of pDCs was not dependent on expression levels of TLR7/9. Furthermore, in vitro experiments revealed that up-regulation of TLR7 response was caused by pre-treatment with type I IFNs, conversely, down-regulation of TLR9 response was caused by pre-treatment with type II IFN.

Conclusions This is the first report demonstrated the differential regulation of TLR7- and TLR9- mediated IFN-α production from pDCs in SLE, namely, caused by priming effects of type I and type II IFNs. Taken together, TLR7-, but not TLR9-, mediated IFN-α production contributes the pathogenesis of SLE, and TLR7 could be a potential therapeutic target for SLE.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.