biostudies-literatureXiao XNIAID NIH HHSNational Institutes of Health559-574https://www.ebi.ac.uk/biostudies/studies/S-EPMC5789412biostudies-literatureUnknown215(2)Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the <i>Il9</i> SEs in Th cells requires OX40-triggered chromatin acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the <i>Il9</i> locus to catalyze H3K27 acetylation. This allows binding of the SE factor Brd4 to organize assembly of the SE complex, which in turn drives robust IL-9 expression and Th9 cell induction. Thus, Th9 cells are strongly induced upon OX40 stimulation, and disruption of SEs abolished Th9 cell induction in vThe Journal of experimental medicineGuidance of super-enhancers in regulation of IL-9 induction and airway inflammation.PMC5789412R01 AI106200R01AI106200R01AI129906R01 AI129906Dou YLi XCLi JFan YLan PZhang XXiao YXiao XLou XMinze LShi XfalseGuidance of super-enhancers in regulation of IL-9 induction and airway inflammation.Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the <i>Il9</i> SEs in Th cells requires OX40-triggered chromatin acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the <i>Il9</i> locus to catalyze H3K27 acetylation. This allows binding of the SE factor Brd4 to organize assembly of the SE complex, which in turn drives robust IL-9 expression and Th9 cell induction. Thus, Th9 cells are strongly induced upon OX40 stimulation, and disruption of SEs abolished Th9 cell induction in v2018-01-01T00:00:00Z2018 Feb2026-05-03T03:33:54.821Z2019-06-06T18:51:22ZS-EPMC57894122933944710.1084/jem.20170928