{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:15:38Z","timestamp":1760145338087,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T00:00:00Z","timestamp":1721433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian National Research, Development and Innovation Fund","award":["OTKA FK-139028","\u00daNKP-23-5","EGA-10"],"award-info":[{"award-number":["OTKA FK-139028","\u00daNKP-23-5","EGA-10"]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology from the Source of the National Research, Development and Innovation Fund","award":["OTKA FK-139028","\u00daNKP-23-5","EGA-10"],"award-info":[{"award-number":["OTKA FK-139028","\u00daNKP-23-5","EGA-10"]}]},{"name":"Thematic Excellence Programme 2021 Health Subprogramme of the Ministry for Innovation and Technology in Hungary","award":["OTKA FK-139028","\u00daNKP-23-5","EGA-10"],"award-info":[{"award-number":["OTKA FK-139028","\u00daNKP-23-5","EGA-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type I interferon (IFN-I) signaling has been shown to be upregulated in systemic sclerosis (SSc). Dysregulated B-cell functions, including antigen presentation, as well as antibody and cytokine production, all of which may be affected by IFN-I signaling, play an important role in the pathogenesis of the disease. We investigated the IFN-I signature in 71 patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and 33 healthy controls (HCs). Activation via Toll-like receptors (TLRs) can influence the IFN-I signaling cascade; thus, we analyzed the effects of the TLR homologue CD180 ligation on the IFN-I signature in B cells. CD180 stimulation augmented the phosphorylation of signal transducer and activator of transcription 1 (STAT1) in dcSSc B cells (p = 0.0123). The expression of IFN-I receptor (IFNAR1) in non-switched memory B cells producing natural autoantibodies was elevated in dcSSc (p = 0.0109), which was enhanced following anti-CD180 antibody treatment (p = 0.0125). Autoantibodies to IFN-Is (IFN-alpha and omega) correlated (dcSSc p = 0.0003, HC p = 0.0192) and were present at similar levels in B cells from dcSSc and HC, suggesting their regulatory role as natural autoantibodies. It can be concluded that factors other than IFN-alpha may contribute to the elevated IFN-I signature of dcSSc B cells, and one possible candidate is B-cell activation via CD180.<\/jats:p>","DOI":"10.3390\/ijms25147933","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T07:57:23Z","timestamp":1721721443000},"page":"7933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Toll-like Receptor Homologue CD180 Ligation of B Cells Upregulates Type I IFN Signature in Diffuse Cutaneous Systemic Sclerosis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-8487","authenticated-orcid":false,"given":"Szabina","family":"Erd\u0151-Bony\u00e1r","sequence":"first","affiliation":[{"name":"Department of Immunology and Biotechnology, Clinical Center, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judit","family":"Rapp","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Clinical Center, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rov\u00e9na","family":"Subicz","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Clinical Center, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krist\u00f3f","family":"Filip\u00e1nits","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Clinical Center, Medical School, University of P\u00e9cs, H-7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0983-2092","authenticated-orcid":false,"given":"T\u00fcnde","family":"Minier","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Clinical Center, Medical School, University of P\u00e9cs, H-7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-2918","authenticated-orcid":false,"given":"G\u00e1bor","family":"Kum\u00e1novics","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Clinical Center, Medical School, University of P\u00e9cs, H-7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Czirj\u00e1k","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Clinical Center, Medical School, University of P\u00e9cs, H-7632 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T\u00edmea","family":"Berki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Clinical Center, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di\u00e1na","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Clinical Center, Medical School, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ji, L., Li, T., Chen, H., Yang, Y., Lu, E., Liu, J., Qiao, W., and Chen, H. 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