{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:46:45Z","timestamp":1787161605481,"version":"build-2736575974"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"12","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["369799452 - TRR237"],"award-info":[{"award-number":["369799452 - TRR237"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["114933180-TR84"],"award-info":[{"award-number":["114933180-TR84"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,3,19]]},"abstract":"<jats:p>\n                    Plasmacytoid dendritic cells (pDCs) produce type I interferons (IFNs) after sensing viral\/bacterial RNA or DNA by toll-like receptor (TLR) 7 or TLR9, respectively. However, aberrant pDCs activation can cause adverse effects on the host and contributes to the pathogenesis of type I IFN-related autoimmune diseases. Here, we show that heparin interacts with the human pDCs-specific blood dendritic cell antigen 2 (BDCA-2) but not with related lectins such as DCIR or dectin-2. Importantly, BDCA-2\u2013heparin interaction depends on heparin sulfation and receptor glycosylation and results in inhibition of TLR9-driven type I IFN production in primary human pDCs and the pDC-like cell line CAL-1. This inhibition is mediated by unfractionated and low-molecular-weight heparin, as well as endogenous heparin from plasma, suggesting that the local blood environment controls the production of IFN-\u03b1 in pDCs. Additionally, we identified an activation-dependent soluble form of BDCA-2 (solBDCA-2) in human plasma that functions as heparin antagonist and thereby increases TLR9-driven IFN-\u03b1 production in pDCs. Of importance, solBDCA-2 levels in the serum were increased in patients with scrub typhus (an acute infectious disease caused by\n                    <jats:italic>Orientia tsutsugamushi<\/jats:italic>\n                    ) compared to healthy control subjects and correlated with anti-dsDNA antibodies titers. In contrast, solBDCA-2 levels in plasma from patients with bullous pemphigoid or psoriasis were reduced. In summary, this work identifies a regulatory network consisting of heparin, membrane-bound and solBDCA-2 modulating TLR9-driven IFN-\u03b1 production in pDCs. This insight into pDCs function and regulation may have implications for the treatment of pDCs-related autoimmune diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2312404121","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:13:40Z","timestamp":1710339220000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":10,"title":["A type I interferon regulatory network for human plasmacytoid dendritic cells based on heparin, membrane-bound and soluble BDCA-2"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-8711","authenticated-orcid":false,"given":"Francisco","family":"Venegas-Solis","sequence":"first","affiliation":[{"name":"Institute for Immunology, Philipps-Universit\u00e4t Marburg, Biomedizinisches Forschungszentrum Marburg, Marburg 35043, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5609-7643","authenticated-orcid":false,"given":"Laura","family":"Staliunaite","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Philipps-Universit\u00e4t Marburg, Biomedizinisches Forschungszentrum Marburg, Marburg 35043, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rudolph","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Philipps-Universit\u00e4t Marburg, Biomedizinisches Forschungszentrum Marburg, Marburg 35043, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina Chan-Song","family":"M\u00fcnch","sequence":"additional","affiliation":[{"name":"Institute of Virology, Philipps-Universit\u00e4t Marburg, Biomedizinisches Forschungszemtrum Marburg, Marburg 35043, 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Venegas P. Yu A. Kaufmann S.-A. Freibert S. Bauer Confocal imaging and microscale thermophoresis dataset from the article: \u201cA novel type I interferon regulatory network for human plasmacytoid dendritic cells based on heparin membrane-bound and soluble type II C-type lectin BDCA-2\u201d Mendeley Data (2023)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2312404121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:15:30Z","timestamp":1710339330000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2312404121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":55,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,3,19]]}},"alternative-id":["10.1073\/pnas.2312404121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2312404121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"assertion":[{"value":"2023-07-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2312404121"}}