{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:10:43Z","timestamp":1791288643977,"version":"4.3.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100013365","name":"west china hospital, sichuan university","doi-asserted-by":"publisher","award":["NO. ZYYC21012"],"award-info":[{"award-number":["NO. ZYYC21012"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the CAMS Innovation Fund for Medical Sciences","award":["CIFMS, 2019-I2M-5-004"],"award-info":[{"award-number":["CIFMS, 2019-I2M-5-004"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2402900"],"award-info":[{"award-number":["2022YFC2402900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NO. 82171829"],"award-info":[{"award-number":["NO. 82171829"]}],"id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"science and technology department of sichuan province","doi-asserted-by":"publisher","award":["NO. 2025YFHZ0205"],"award-info":[{"award-number":["NO. 2025YFHZ0205"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>\n                    Recurrent aphthous stomatitis (RAS) is a common chronic oral disease with unclear pathogenesis. Chronic inflammation associated with RAS has been linked to the dysregulation of local immune responses. We used a murine model of acetic acid\u2013induced chemical stomatitis (CS) to assess changes in the systemic and local immune environments of CS mice relative to healthy mice. Flow cytometry revealed a significant increase in neutrophil infiltration and elevated proportions of Th1 (CD4\n                    <jats:sup>+<\/jats:sup>\n                    IFN-\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    ) and Th17 (CD4\n                    <jats:sup>+<\/jats:sup>\n                    IL-17a\n                    <jats:sup>+<\/jats:sup>\n                    ) cells in the lingual mucosa of CS mice 7 d after CS induction, indicating an active inflammatory response in the CS immune microenvironment. Given that Th17 cells indirectly recruit neutrophils, we used\n                    <jats:italic toggle=\"yes\">Rorc<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice to evaluate the effects of Th17 cell depletion. Neutrophil infiltration was markedly reduced, and decreased tissue damage was observed in the lingual mucosa of\n                    <jats:italic toggle=\"yes\">Rorc<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice, as confirmed by hematoxylin and eosin staining. To further investigate the mechanism underlying Th17 cell generation in stomatitis, we induced CS in\n                    <jats:italic toggle=\"yes\">Il6ra<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice, which exhibited significantly reduced inflammatory cell infiltration and ulcer severity in the lingual mucosa. Treatment with an anti-Ly6G antibody treatment, which can directly target and deplete neutrophils, also significantly reduced local inflammation in the CS mouse immune microenvironment and diminished Th1 and Th17 cell infiltration, indicating a positive feedback loop between Th17 cells and neutrophils in stomatitis. In conclusion, the IL-6\u2013Th17\u2013neutrophil axis plays a critical role in stomatitis pathogenesis, suggesting that targeting this axis could present a novel immunotherapeutic strategy for alleviating mucosal damage in patients with RAS.\n                  <\/jats:p>","DOI":"10.1177\/00220345251338031","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T01:24:14Z","timestamp":1750987454000},"page":"1373-1384","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Targeting the IL-6\u2013Th17\u2013Neutrophil Axis Reduces Local Inflammation in Stomatitis"],"prefix":"10.1177","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6862-8175","authenticated-orcid":false,"given":"Z.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China"},{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5665-0139","authenticated-orcid":false,"given":"H.","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. 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