{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:17:09Z","timestamp":1788445029337,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020477","name":"Edward Via College of Osteopathic Medicine","doi-asserted-by":"publisher","award":["461722"],"award-info":[{"award-number":["461722"]}],"id":[{"id":"10.13039\/100020477","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    TCR\u03b1\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    double negative T (TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    DNT) cells are highly accumulated in human and murine lupus, although the origin and function of TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    DNT cells remains largely elusive and controversy. Remarkably, conditional deletion of\n                    <jats:italic>Egr2<\/jats:italic>\n                    in lymphocytes significantly reduced TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    NK1.1\n                    <jats:sup>\u2212<\/jats:sup>\n                    DNT cells, the dominant DNT type in B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    mice. TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    DNT cells of B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    mice surprisingly had a lower expression of IFN\u03b3, IL\u201017, and IL\u201010 compared to normal B6 mice, which was likely due to high CD138 expression in the TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    DNT cells of B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    mice. Conditionally deleting\n                    <jats:italic>Egr2<\/jats:italic>\n                    in B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    mice increased IFN\u03b3 and IL\u201010, but not IL\u201017 in TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    DNT cells.\n                    <jats:italic>Egr2<\/jats:italic>\n                    deletion suppressed IL\u201017 expression in TCR\u03b3\u03b4\n                    <jats:sup>+<\/jats:sup>\n                    DNT cells, the major IL\u201017\u2010expressing DNT cells in B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    mice. The scRNA\u2010seq analysis of DNT cells from\n                    <jats:italic>Egr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212<\/jats:italic>\n                      \/\u2212\n                    <\/jats:sup>\n                    B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    (CD2\u2010Cre\n                    <jats:italic>Egr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212<\/jats:italic>\n                      \/\u2212\n                    <\/jats:sup>\n                    B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    , EK) and control\n                    <jats:italic>Egr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>fl\/fl<\/jats:italic>\n                    <\/jats:sup>\n                    B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    (EF) mice revealed a striking segregation of DNT clusters with distinct transcriptional profiles, identified as EK_dominant and EF_dominant DNT clusters.\n                    <jats:italic>Egr2<\/jats:italic>\n                    deletion in B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    mice seemingly normalised Helios, Ly6C, and Ly6A\/E expression to levels similar to B6 mice, implying that inhibition of EGR2 can effectively correct the abnormalities in DNT cells of B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    mice. Further, we found that conditional\n                    <jats:italic>Egr2<\/jats:italic>\n                    deletion reduced TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    DN thymocytes in B6\/\n                    <jats:italic>lpr<\/jats:italic>\n                    mice and suppressed DNT\u2010cell generation from in\u00a0vitro cultured splenic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, suggesting that EGR2 might promote TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    DNT cells in\n                    <jats:italic>lpr<\/jats:italic>\n                    mice at both the thymic and peripheral stages. Together, this study is the first to reveal a critical role of EGR2 in regulating the expansion, heterogeneity, and function of TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    DNT cells in lupus mice.\n                  <\/jats:p>","DOI":"10.1111\/imm.70162","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:54:47Z","timestamp":1782089687000},"page":"224-235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Transcription Factor\n                    <scp>EGR2<\/scp>\n                    Plays a Central Role in the Expansion and Function of\n                    <scp>TCR\u03b1\u03b2<\/scp>\n                    <sup>+<\/sup>\n                    <scp>CD4<\/scp>\n                    <sup>\u2212<\/sup>\n                    <scp>CD8<\/scp>\n                    <sup>\u2212<\/sup>\n                    Double Negative T Cells in lpr Lupus Mice"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1074-8974","authenticated-orcid":false,"given":"Rujuan","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology Virginia\u2010Maryland College of Veterinary Medicine (VMCVM), Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology Virginia\u2010Maryland College of Veterinary Medicine (VMCVM), Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Heid","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology Virginia\u2010Maryland College of Veterinary Medicine (VMCVM), Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Pathobiology Virginia\u2010Maryland College of Veterinary Medicine (VMCVM), Virginia Tech  Blacksburg Virginia USA"},{"name":"Via Virginia College of Osteopathic Medicine  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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