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Adv."],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>\n                    T helper 17 (T\n                    <jats:sub>H<\/jats:sub>\n                    17) lineage is governed by canonical transcriptional factors and plays a pivotal role in the pathogenesis of autoimmune diseases in both mice and humans. However, the precise orchestration of this transcriptional program remains poorly understood. Here, we identified a positive correlation between the expression of Dhx9, a nuclear helicase, and T\n                    <jats:sub>H<\/jats:sub>\n                    17 lineage during the progression of autoimmune diseases. Conditional deletion of\n                    <jats:italic toggle=\"yes\">Dhx9<\/jats:italic>\n                    in T cells significantly reduced T\n                    <jats:sub>H<\/jats:sub>\n                    17 differentiation and ameliorated the symptoms in mouse models of experimental autoimmune encephalomyelitis (EAE) and rheumatoid arthritis (RA). Mechanistically, Dhx9 was essential for increasing chromatin accessibility at the\n                    <jats:italic toggle=\"yes\">Rorc<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Il17<\/jats:italic>\n                    loci, thereby facilitating the binding of canonical factors SMAD2, SMAD3, STAT3 (signal transducer and activator of transcription 3), and IRF4 (interferon regulatory factor 4) to drive the transcription of these two core T\n                    <jats:sub>H<\/jats:sub>\n                    17-specific genes. We additionally identified Nono as an uncharacterized regulator of T\n                    <jats:sub>H<\/jats:sub>\n                    17 differentiation that acts dependent on its interaction with Dhx9. Meanwhile, IL-6 (interleukin-6)\u2013STAT3 signaling promotes T\n                    <jats:sub>H<\/jats:sub>\n                    17 cell differentiation by up-regulating\n                    <jats:italic toggle=\"yes\">Dhx9<\/jats:italic>\n                    expression. We identified a potential small-molecule inhibitor of Dhx9, punicalagin, which effectively suppressed T\n                    <jats:sub>H<\/jats:sub>\n                    17 differentiation and EAE progression. These findings uncover a mechanism orchestrating the transcriptional program of T\n                    <jats:sub>H<\/jats:sub>\n                    17 lineage commitment and highlight its therapeutic potential for autoimmune disease intervention.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb9679","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:59:07Z","timestamp":1778867947000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Helicase A determines the transcription program of T\n                    <sub>H<\/sub>\n                    17 lineage differentiation and autoimmunity"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8358-9141","authenticated-orcid":true,"given":"Yanhong","family":"Su","sequence":"first","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an, Shaanxi, China."},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University, Xi\u2019an, Shaanxi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6892-9512","authenticated-orcid":true,"given":"Anjun","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an, Shaanxi, China."},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University, Xi\u2019an, Shaanxi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2856-7670","authenticated-orcid":true,"given":"Xiaoran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an, Shaanxi, China."},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University, Xi\u2019an, Shaanxi, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8843-9426","authenticated-orcid":true,"given":"Yanan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Liver Surgery and Transplantation and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1261-763X","authenticated-orcid":true,"given":"Huanxin","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an, Shaanxi, 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