{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:23:38Z","timestamp":1790835818095,"version":"4.1.0"},"reference-count":45,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"821","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,10,22]]},"abstract":"<jats:p>\n                    Nonalcoholic steatohepatitis (NASH) is a chronic, inflammatory form of nonalcoholic fatty liver disease (NAFLD) that frequently progresses to cirrhosis and hepatocellular carcinoma (HCC). However, the role of various immune cells in switching from NAFLD to NASH remains elusive. Here, we took an unbiased single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) approach to investigate the cellular composition, gene expression profiling, and causative roles of immune cells in NASH development. T helper 17 (T\n                    <jats:sub>H<\/jats:sub>\n                    17) cells were identified as the most abundant subpopulation of immune cells in mouse livers with NASH. Further analysis of scATAC-seq data and single-cell RNA sequencing (scRNA-seq) data from the GEO database showed that human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1) is a critical transcription factor (TF) regulating T\n                    <jats:sub>H<\/jats:sub>\n                    17 cell differentiation and cytokine production. Specific knockout of\n                    <jats:italic toggle=\"yes\">Hivep1<\/jats:italic>\n                    in IL-17A\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in mice showed impairment of T\n                    <jats:sub>H<\/jats:sub>\n                    17 cell differentiation and alleviation of NASH development. Mechanistically, HIVEP1 transcriptionally regulated ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme of polyamine metabolism, to modulate T\n                    <jats:sub>H<\/jats:sub>\n                    17 cell differentiation and cytokine production. Consequently, pharmacological inhibition of ODC1 decreased cytokine production, alleviated inflammation, and prevented the NAFLD-to-NASH transition. Together, our findings elucidate the role of polyamine metabolism in T\n                    <jats:sub>H<\/jats:sub>\n                    17 cell\u2013mediated NASH development and identify potential therapeutic targets for the effective treatment of NASH.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adn1150","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:59:08Z","timestamp":1761155948000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["HIVEP1 aggravates NASH by reprogramming polyamine metabolism in T\n                    <sub>H<\/sub>\n                    17 cells"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7964-4559","authenticated-orcid":true,"given":"Yidan","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8922-3766","authenticated-orcid":true,"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3612-9792","authenticated-orcid":true,"given":"Maoxiao","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8972-3702","authenticated-orcid":true,"given":"Jianxiong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 250012 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangmiao","family":"Duan","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 250012 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiru","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Second Hospital, Cheeloo College of Medicine, Shandong University, 250033 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Qilu Hospital of Shandong University Dezhou Hospital, 253000 Dezhou, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, 250012 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4607-311X","authenticated-orcid":true,"given":"Jiaying","family":"Yao","sequence":"additional","affiliation":[{"name":"Annoroad Gene Technology (Beijing) Co. Ltd, 100176 Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-5120","authenticated-orcid":true,"given":"Zan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Annoroad Gene Technology (Beijing) Co. Ltd, 100176 Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4864-1870","authenticated-orcid":true,"given":"Xu","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, 171 65 Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-0131","authenticated-orcid":true,"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, First Affiliated Hospital of Shandong First Medical University and the Shandong Provincial Qianfoshan Hospital, 250014 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1308-0065","authenticated-orcid":true,"given":"Yihai","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, 171 65 Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-8752","authenticated-orcid":true,"given":"Yunshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 250021 Jinan, Shandong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14362"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2019.1683817"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2018.12.026"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.012"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00639-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501175"},{"key":"e_1_3_2_8_2","first-page":"916","article-title":"Interleukin-17-mediated inflammation promotes nonalcoholic fatty liver disease in mice with regulation of M1-type macrophage polarization","volume":"26","author":"Yang Y.","year":"2018","unstructured":"Y. Yang, C. Y. Han, Q. B. Guan, S. L. Ruan, Interleukin-17-mediated inflammation promotes nonalcoholic fatty liver disease in mice with regulation of M1-type macrophage polarization. Zhonghua Gan Zang Bing Za Zhi 26, 916\u2013921 (2018).","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.05.020"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe6474"},{"key":"e_1_3_2_11_2","first-page":"22","article-title":"Role of polyamines in immune cell functions","volume":"6","author":"Hesterberg R. S.","year":"2018","unstructured":"R. S. Hesterberg, J. L. Cleveland, P. K. Epling-Burnette, Role of polyamines in immune cell functions. Med. Sci. 6, 22 (2018).","journal-title":"Med. 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Ryu, J. Kim, D. Kim, J. E. Lee, Y. Chung, Cellular and molecular links between autoimmunity and lipid metabolism. Mol. Cells 42, 747\u2013754 (2019).","journal-title":"Mol. 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