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However, the complete repertoire of transcriptional regulators controlling Il17a gene transcription and Th17 commitment remains incompletely defined. Here, we identify zinc finger protein 335 (ZFP335) as a critical regulator of Th17 differentiation. Mechanistically, ZFP335 directly binds and activates the Mybl2 promoter, and the resulting MYBL2 protein cooperates with ROR\u03b3t to drive Il17a transcription. Genetic ablation of Zfp335 attenuated imiquimod-induced psoriasis-like skin inflammation and diminished Th17 cell responses in vivo. Notably, Mybl2 deficiency phenocopied these protective effects. Collectively, these findings establish a ZFP335\u2013MYBL2\u2013IL17A transcriptional axis that governs Th17 differentiation and identify this pathway as a potential therapeutic target for Th17-mediated inflammatory diseases.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag260","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:53:27Z","timestamp":1790625207000},"source":"Crossref","is-referenced-by-count":0,"title":["ZFP335\u2013MYBL2 transcriptional axis orchestrates Th17 cell differentiation and psoriatic inflammation"],"prefix":"10.1093","volume":"215","author":[{"given":"Wenhua","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Key Laboratory for ImmunoHealth of Shaanxi Province, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Key Laboratory for ImmunoHealth of Shaanxi Province, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi,","place":["China"]},{"name":"Institute of Infection and Immunity, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, 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