Psarras, A, Alase, A, Antanaviciute, A et al. (6 more authors) (2020) Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity. Nature Communications, 11. 6149. ISSN 2041-1723
Abstract
Autoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons have a crucial role in the progression to established autoimmune diseases. The cellular source and regulation in disease initiation of these cytokines is not clear, but plasmacytoid dendritic cells have been thought to contribute to excessive type I interferon production. Here, we show that in preclinical autoimmunity and established systemic lupus erythematosus, plasmacytoid dendritic cells are not effector cells, have lost capacity for Toll-like-receptor-mediated cytokine production and do not induce T cell activation, independent of disease activity and the blood interferon signature. In addition, plasmacytoid dendritic cells have a transcriptional signature indicative of cellular stress and senescence accompanied by increased telomere erosion. In preclinical autoimmunity, we show a marked enrichment of an interferon signature in the skin without infiltrating immune cells, but with interferon-κ production by keratinocytes. In conclusion, non-hematopoietic cellular sources, rather than plasmacytoid dendritic cells, are responsible for interferon production prior to clinical autoimmunity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Clinical Musculoskeletal Medicine (LIRMM) (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Experimental Musculoskeletal Medicine (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds) |
Funding Information: | Funder Grant number NIHR National Inst Health Research CS-2013-13-032 NIHR National Inst Health Research DRF-2014-07-155 MRC (Medical Research Council) MR/M01665X/1 - R118193 Astra Zeneca D2287C00002 Lupus UK Not Known Medical Research Foundation MRF-159-0003-ELP-VITAL Lupus UK none provided |
Depositing User: | Symplectic Publications |
Date Deposited: | 30 Nov 2020 12:19 |
Last Modified: | 26 Jan 2021 13:39 |
Status: | Published |
Publisher: | Nature Research |
Identification Number: | 10.1038/s41467-020-19918-z |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:168511 |