{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:04:19Z","timestamp":1791522259383,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T00:00:00Z","timestamp":1494460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2017,8]]},"abstract":"Signal transducer and activator of transcription 3 (STAT<\/jats:styled-content>3) is a key signaling protein in the skeletal system as well as in the immune system. Accumulating evidence demonstrates that the inflammatory response is deeply involved in the healing process of bone fractures, but how the immune system is regulated during this process is unclear. In this study, we examined STAT<\/jats:styled-content>3\u2010mediated regulation of immunity in adult patients with closed tibia fracture. In all patients, the expression and activation of STAT<\/jats:styled-content>3 peaked at around day 7 to day 14 after surgery, and gradually decreased during the rest of the healing period. At day 7 (peak STAT<\/jats:styled-content>3 expression and phosphorylation), the CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> T cells from bone fracture patients presented the highest level of STAT<\/jats:styled-content>3 activation among lymphocyte subsets. Therefore, we investigated the role of STAT<\/jats:styled-content>3 in CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> T cells. The level of FOXP<\/jats:styled-content>3 expression by CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> T cells was directly correlated with the level of STAT<\/jats:styled-content>3 phosphorylation in these cells. The level of STAT<\/jats:styled-content>3 phosphorylation in CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> T cells was also inversely correlated with the level of IFN<\/jats:styled-content>\u2010\u03b3 and TNF<\/jats:styled-content>\u2010\u03b1 secretion in peripheral blood mononuclear cells. Inhibition of STAT<\/jats:styled-content>3 significantly suppressed FOXP<\/jats:styled-content>3 and IL<\/jats:styled-content>\u201010 expression by CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> T cells, as well as the ability of CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> T cells to suppress T\u2010cell IFN<\/jats:styled-content>\u2010\u03b3 and TNF<\/jats:styled-content>\u2010\u03b1 secretion. Furthermore, early healers patients presented significantly higher STAT<\/jats:styled-content>3 expression and phosphorylation than late healers, possibly due to the higher IL<\/jats:styled-content>\u20106 and IL<\/jats:styled-content>\u201010 levels in the serum of early healing patients. Together, these data demonstrated that STAT<\/jats:styled-content>3 was beneficial to bone fracture healing, possibly by enhancing Treg\u2010mediated suppression of counteracting inflammations, and suggested that STAT<\/jats:styled-content>3 could be used as a prognostic marker to identify otherwise undistinguishable patients at risk of developing delayed union or nonunion.<\/jats:p>","DOI":"10.1111\/apm.12706","type":"journal-article","created":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T15:45:58Z","timestamp":1494517558000},"page":"752-760","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["STAT<\/scp>3 promotes bone fracture healing by enhancing the FOXP<\/scp>3 expression and the suppressive function of regulatory T cells"],"prefix":"10.1111","volume":"125","author":[{"given":"Guojing","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Orthopedics Jinling Hospital, Nanjing University School of Medicine Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Nanjing Gaochun People's Hospital Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfan","family":"Ti","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Jinling Hospital, Nanjing University School of Medicine Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Jinling Hospital, Nanjing University School of Medicine Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Jinling Hospital, Nanjing University School of Medicine Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianning","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Jinling Hospital, Nanjing University School of Medicine Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Jinling Hospital, Nanjing University School of Medicine Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1226"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073687"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06096"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.041816fl"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0237137100"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.02.074"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.4161\/jkst.23930"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.04.020"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40634-014-0017-6"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-0266(02)00072-4"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650100818"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903841"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12439"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.1727"},{"key":"e_1_2_6_16_1","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1210\/endo.137.4.8625884","article-title":"Activation 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