{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:25:13Z","timestamp":1787066713245,"version":"build-2736575974"},"reference-count":38,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"unspecified","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010823","name":"Tore Nilsons Stiftelse f\u00f6r Medicinsk Forskning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010823","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rheumatology Foundations at Karolinska Institutet"},{"DOI":"10.13039\/501100014034","name":"Foundation for Research in Rheumatology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006285","name":"Magnus Bergvalls Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006285","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007435","name":"\u00c5ke Wiberg Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007435","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007857","name":"Stiftelsen Konung Gustaf V:s 80-\u00e5rsfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009800","name":"Stiftelsen Professor Nanna Svartz Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009800","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011727","name":"Stockholm l\u00e4ns landsting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004722","name":"Stiftelsen Lars Hiertas Minne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004722","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,4,24]]},"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Activation of the type I interferon (IFN) pathway and autoreactive B cells are key immunopathogenic features of systemic lupus erythematosus (SLE), primary Sj\u00f6gren\u2019s disease (pSjD) and systemic sclerosis (SSc). TANK-binding kinase 1 (TBK1) is a mediator of type I IFN and essential during B cell development in mice. We investigated the properties of the TBK1 inhibitor amlexanox in systemic autoimmune diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The effects of amlexanox on peripheral blood mononuclear cells (PBMCs) stimulated with Imiquimod, CpG-A, Poly:IC, G3-YsD and 3p-hpRNA were assessed. B cells from healthy controls and patients with SLE, pSjD and SSc were cultured with CD40L, IL-21, IFN, B cell activating factor (BAFF) and amlexanox. Differentiation into CD38\n                      <jats:sup>high<\/jats:sup>\n                      CD27\n                      <jats:sup>high<\/jats:sup>\n                      CD138\n                      <jats:sup>+\/-<\/jats:sup>\n                      cells, proliferation, and IgM and IgG production were measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Amlexanox inhibited production of type I IFN induced through endosomal and cytosolic routes in PBMCs. Likewise, supernatants from amlexanox-treated cells did not induce expression of\n                      <jats:italic>BAFF<\/jats:italic>\n                      and\n                      <jats:italic>MX1<\/jats:italic>\n                      . Amlexanox inhibited spontaneous\n                      <jats:italic>MX1<\/jats:italic>\n                      expression in PBMCs from SLE, pSjD and SSc patients. Immunohistochemical staining confirmed expression of the TBK1 protein in pSjD salivary glands. Using a B cell differentiation assay, addition of amlexanox decreased B cell proliferation and differentiation into CD27\n                      <jats:sup>high<\/jats:sup>\n                      CD38\n                      <jats:sup>high<\/jats:sup>\n                      CD138\n                      <jats:sup>+\/-<\/jats:sup>\n                      plasmablasts and plasma cells. Correspondingly, production of IgM and IgG was suppressed. The observations were corroborated in B cells from patients with SLE, pSjD and SSc.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings demonstrate inhibitory effects of amlexanox on type I IFN production and B cell differentiation in primary human cells. Inhibition of TBK1 could potentially be a therapeutic option for the treatment of type I IFN-driven systemic inflammatory diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-005351","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T04:10:20Z","timestamp":1746677420000},"page":"e005351","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Amlexanox inhibits production of type I interferon and suppresses B cell differentiation\n                    <i>in vitro<\/i>\n                    : a possible therapeutic option for systemic lupus erythematosus and other systemic inflammatory diseases"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2410-2015","authenticated-orcid":false,"given":"Albin","family":"Bj\u00f6rk","sequence":"first","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"},{"name":"Center for Rheumatology, Academic Specialist Center, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Javad","family":"Wahadat","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"Department of Pediatric Rheumatology, Sophia Children\u2019s Hospital, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0815-6488","authenticated-orcid":false,"given":"Maria","family":"S\u00e1nchez-Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8013-7442","authenticated-orcid":false,"given":"Merijn","family":"Braams","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5780-9271","authenticated-orcid":false,"given":"Jasper","family":"Rip","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"},{"name":"MS Center ErasMS, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-9797","authenticated-orcid":false,"given":"Sander J","family":"van Tilburg","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6393-7347","authenticated-orcid":false,"given":"Cornelia G","family":"van Helden-Meeuwsen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1964-352X","authenticated-orcid":false,"given":"Sylvia","family":"Kamphuis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Sophia Children\u2019s Hospital, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry P P","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Bioinformatics, Erasmus 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