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We focused on investigating the role and mechanism of DNTs in regulating the Th9 cells differentiation in liver fibrosis. In our results, among patients with liver fibrosis, the proportions of peripheral blood DNTs and Th9 cells were up\u2010regulated and positively correlated. While promoting the progression of liver fibrosis in mice, DNTs could elevate the proportion of Th9 cells and activate the TNFR2\u2010STAT5\u2010NF\u2010\u03baB pathway. The use of IL\u20109 and TNF\u2010\u03b1 monoclonal antibodies (mAbs) inhibited the effect of DNTs and lowered the proportion of Th9 cells in tissues. In vitro experiments showed that DNTs could promote the Th9 cells differentiation of Naive T cells, while TNF\u2010\u03b1 mAbs could inhibit such effect of DNTs to lower the proportion of Th9 cells. We found that DNTs can activate TNFR2\u2010STAT5\u2010NF\u2010\u03baB pathway by secreting TNF\u2010\u03b1, thereby promoting the Th9 Cells differentiation to facilitate the progression of liver fibrosis. There is interaction between DNTs and Th9 cells.<\/jats:p>","DOI":"10.1111\/liv.15612","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T09:25:25Z","timestamp":1685438725000},"page":"1604-1613","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Double\u2010negative T cells regulate the progression of liver fibrosis through Th9 cells differentiation"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-580X","authenticated-orcid":false,"given":"Chenyang","family":"Han","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Pei","sequence":"additional","affiliation":[{"name":"Jilin Agricultural University  Changchun 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