{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:40:29Z","timestamp":1790804429300,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Toll\u2010like receptors (TLR) control the activation of dendritic cells that prime CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in draining lymph nodes, where these T cells then undergo massive clonal expansion. The mechanisms controlling this clonal T cell expansion are poorly defined. Using the CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2010mediated disease experimental autoimmune encephalomyelitis (EAE), we show here that this process is markedly suppressed when TLR9 signaling is increased, without noticeably affecting the transcriptome of primed T cells, indicating a purely quantitative effect on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell expansion. Addressing the underpinning mechanisms revealed that CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell expansion was preceded and depended on the accumulation of neutrophils in lymph nodes a few days after immunization. Underlying the importance of this immune regulation pathway, blocking neutrophil accumulation in lymph nodes by treating mice with a TLR9 agonist inhibited EAE progression in mice with defects in regulatory T cells or regulatory B cells, which otherwise developed a severe chronic disease. Collectively, this study demonstrates the key role of neutrophils in the quantitative regulation of antigen\u2010specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell expansion in lymph nodes, and the counter\u2010regulatory role of TLR signaling in this process.\n                  <\/jats:p>","DOI":"10.1002\/eji.202250059","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T05:33:37Z","timestamp":1669959217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Toll\u2010like receptors control the accumulation of neutrophils in lymph nodes that expand CD4\n                    <sup>+<\/sup>\n                    T cells during experimental autoimmune encephalomyelitis"],"prefix":"10.1002","volume":"53","author":[{"given":"Ping","family":"Shen","sequence":"first","affiliation":[{"name":"Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute  Germany"},{"name":"Department of Rheumatology and Clinical Immunology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  10117 Berlin Germany"},{"name":"Stem Cell and Biotherapy Engineering Research Center of Henan Province, College of Life Sciences and Technology Xinxiang Medical University  Xinxiang 453003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madlen","family":"Rother","sequence":"additional","affiliation":[{"name":"Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik","family":"Stervbo","sequence":"additional","affiliation":[{"name":"Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky","family":"Lampropoulou","sequence":"additional","affiliation":[{"name":"Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute  Germany"},{"name":"Department of Microbiology, Medical School National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Calderon\u2010Gomez","sequence":"additional","affiliation":[{"name":"Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-8700","authenticated-orcid":false,"given":"Toralf","family":"Roch","sequence":"additional","affiliation":[{"name":"Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Hilgenberg","sequence":"additional","affiliation":[{"name":"Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute  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