{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:09Z","timestamp":1790553609505,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100006315","name":"ReumaNederland","doi-asserted-by":"publisher","award":["15-2-401"],"award-info":[{"award-number":["15-2-401"]}],"id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>TNF is important in immune-mediated inflammatory diseases, including spondyloarthritis (SpA). Transgenic (tg) mice overexpressing transmembrane TNF (tmTNF) develop features resembling human SpA. Furthermore, both tmTNF tg mice and SpA patients develop ectopic lymphoid aggregates, but it is unclear whether these contribute to pathology. Therefore, we characterized the lymphoid aggregates in detail and studied potential alterations in the B and T cell lineage in tmTNF tg mice. Lymphoid aggregates developed in bone marrow (BM) of vertebrae and near the ankle joints prior to the first SpA features and displayed characteristics of ectopic lymphoid structures (ELS) including presence of B cells, T cells, germinal centers, and high endothelial venules. Detailed flow cytometric analyses demonstrated more germinal center B cells with increased CD80 and CD86 expression, along with significantly more T follicular helper, T follicular regulatory, and T regulatory cells in tmTNF tg BM compared with non-tg controls. Furthermore, tmTNF tg mice exhibited increased IgA serum levels and significantly more IgA+ plasma cells in the BM, whereas IgA+ plasma cells in the gut were not significantly increased. In tmTNF tg \u00d7 TNF-RI\u2212\/\u2212 mice, ELS were absent, consistent with reduced disease symptoms, whereas in tmTNF tg \u00d7 TNF-RII\u2212\/\u2212 mice, ELS and clinical symptoms were still present. Collectively, these data show that tmTNF overexpression in mice results in osteitis and ELS formation in BM, which may account for the increased serum IgA levels that are also observed in human SpA. These effects are mainly dependent on TNF-RI signaling and may underlie important aspects of SpA pathology.<\/jats:p>","DOI":"10.4049\/jimmunol.2100512","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T17:10:43Z","timestamp":1632503443000},"page":"2337-2346","source":"Crossref","is-referenced-by-count":6,"title":["Overexpression of Transmembrane TNF Drives Development of Ectopic Lymphoid Structures in the Bone Marrow and B Cell Lineage Alterations in Experimental Spondyloarthritis"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4554-4760","authenticated-orcid":false,"given":"Merlijn H","family":"Kaaij","sequence":"first","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]},{"name":"Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Rip","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim C M","family":"Jeucken","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]},{"name":"Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6213-9372","authenticated-orcid":false,"given":"Yik Y","family":"Kan","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]},{"name":"Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte C N","family":"van Rooijen","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]},{"name":"Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Job","family":"Saris","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]},{"name":"Tytgat Institute for 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Duivenvoorde","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]},{"name":"Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5447-0839","authenticated-orcid":false,"given":"Martijn A","family":"Nolte","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam , Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi W","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus University Medical Center , Rotterdam 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