{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:19:39Z","timestamp":1789633179346,"version":"build-2803163510"},"reference-count":68,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:00Z","timestamp":1750464000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022115","name":"Dutch Arthritis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022115","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Murine studies have demonstrated that lymph node fibroblasts can present self-antigens via major histocompatibility complex class II molecules, inducing functional regulatory T cells and contributing to peripheral tolerance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To investigate this phenomenon in humans, we developed an in vitro system co-culturing human lymph node fibroblasts with autologous CD4+ T cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our results reveal that lymph node fibroblasts upregulate human leukocyte antigen-DR (HLA-DR) upon contact with CD4+ T cells and maintain FoxP3\u2005+\u2005regulatory T cells. This maintenance is lost upon blockade of HLA-DR or interleukin-2, and regulatory T cells are lost in the absence of lymph node fibroblasts. Furthermore, we demonstrate that lymph node fibroblasts directly isolated from rheumatoid arthritis patients exhibit a significant reduction in the frequency of HLA-DR\u2005+\u2005cells compared to those from individuals at risk of developing the disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These findings highlight a crucial role for HLA-DR-expressing lymph node fibroblasts in maintaining peripheral tolerance within lymph nodes, a function that may be impaired in autoimmunity. Our study provides novel insights into the intricate cellular interactions within human lymph nodes and their potential implications in autoimmune disorders, opening new avenues for understanding and potentially treating these conditions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cei\/uxaf042","type":"journal-article","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T18:07:45Z","timestamp":1751134065000},"source":"Crossref","is-referenced-by-count":1,"title":["HLA-DR expressing lymph node fibroblasts maintain FoxP3+ regulatory T cells and are reduced in rheumatoid arthritis"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8185-2501","authenticated-orcid":false,"given":"Aoife M","family":"O\u2019Byrne","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Location AMC, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Rheumatology and Immunology 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Immunology , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5065-7439","authenticated-orcid":false,"given":"Janne W","family":"Bolt","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Location AMC, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Rheumatology and Immunology Centre (ARC) , Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam UMC, Location AMC, University of Amsterdam, Laboratory for Experimental Immunology , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen G H","family":"van de Sande","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Location AMC, University of Amsterdam , Amsterdam ,","place":["The Netherlands"]},{"name":"Amsterdam Rheumatology 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