{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:05:06Z","timestamp":1788199506122,"version":"build-2803163510"},"reference-count":62,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20240813170459001"],"award-info":[{"award-number":["JCYJ20240813170459001"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To characterise neutrophil extracellular traps (NETs) and their regulatory mechanisms in pulpitis, and to evaluate the therapeutic potential of targeting neutrophil subsets:<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Transcriptomic analyses of microarray (GSE92681) and single\u2010cell RNA sequencing datasets (GSE274562, GSE280528) were performed to delineate immune heterogeneity and intercellular communication. HL\u201060\u2010derived neutrophils, THP\u20101 macrophages, and human Dental Pulp Cells (hDPCs) were used for in\u00a0vitro assays of NETs induction, chemotaxis, osteogenic differentiation and immunofluorescence. Healthy male Sprague\u2013Dawley rats (7\u20138\u2009weeks,\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20095\/group) were used to establish pulpitis models treated with the CXCR2 inhibitor AZD5069 (S6645, Selleck), followed by histology, immunostaining, and micro\u2010CT analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptomic profiling revealed significant enrichment of NETs\u2010related pathways in inflamed pulp. Immunofluorescence confirmed MPO\n                      <jats:sup>+<\/jats:sup>\n                      \/CitH3\n                      <jats:sup>+<\/jats:sup>\n                      NETs in inflamed tissues, while NETs significantly impaired hDPCs osteogenesis in\u00a0vitro. Single\u2010cell analysis identified a distinct CXCR2\n                      <jats:sup>+<\/jats:sup>\n                      neutrophil subset (CXCR2\n                      <jats:sup>+<\/jats:sup>\n                      Neu), representing a mature pro\u2010inflammatory population specialised in NETs release. Cell\u2013cell interaction analysis highlighted CXCL8\u2013CXCR2 signalling from pro\u2010inflammatory macrophages as the major driver of neutrophil recruitment and NETs formation. In\u00a0vitro, M1 macrophages enhanced neutrophil chemotaxis and NETs release, whereas NETs reciprocally promoted M1\u2010like polarisation. In\u00a0vivo, CXCR2 inhibition markedly reduced neutrophil infiltration and NETs release, while promoting reparative mineralization in rat pulpitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      CXCR2\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils act as a pro\u2010inflammatory subset in pulpitis, driving NETs release through macrophage\u2010derived signals. Inhibition of CXCR2 attenuates inflammation and enhances dentine repair, supporting CXCR2 as a promising therapeutic target for immune modulation in pulpitis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70098","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T08:13:08Z","timestamp":1769501588000},"page":"819-835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>CXCR2<\/scp>\n                    <sup>+<\/sup>\n                    Neutrophils Drive Neutrophil Extracellular Traps Formation and Exacerbate Pulpitis in Rats: An In\u00a0Vitro and In\u00a0Vivo Laboratory Investigation"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0756-2746","authenticated-orcid":false,"given":"Ruilin","family":"Zhang","sequence":"first","affiliation":[{"name":"Nanfang Hospital Southern Medical University  Guangzhou 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