STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus

Yongyao Fu, Jocelyn Wang, Gayathri Panangipalli, Benjamin J. Ulrich, Byunghee Koh, Chengxian Xu, Rakshin Kharwadkar, Xiaona Chu, Yue Wang, Hongyu Gao, Wenting Wu, Jie Sun, Robert S. Tepper, Baohua Zhou, Sarath Chandra Janga, Kai Yang and Mark H. Kaplan ()
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Yongyao Fu: Indiana University School of Medicine
Jocelyn Wang: Indiana University School of Medicine
Gayathri Panangipalli: Indiana University-Purdue University
Benjamin J. Ulrich: Indiana University School of Medicine
Byunghee Koh: Indiana University School of Medicine
Chengxian Xu: Indiana University School of Medicine
Rakshin Kharwadkar: Indiana University School of Medicine
Xiaona Chu: Indiana University School of Medicine
Yue Wang: Indiana University School of Medicine
Hongyu Gao: Indiana University School of Medicine
Wenting Wu: Indiana University School of Medicine
Jie Sun: Mayo Clinic
Robert S. Tepper: Indiana University School of Medicine
Baohua Zhou: Indiana University School of Medicine
Sarath Chandra Janga: Indiana University-Purdue University
Kai Yang: Indiana University School of Medicine
Mark H. Kaplan: Indiana University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract T helper cell differentiation requires lineage-defining transcription factors and factors that have shared expression among multiple subsets. BATF is required for development of multiple Th subsets but functions in a lineage-specific manner. BATF is required for IL-9 production in Th9 cells but in contrast to its function as a pioneer factor in Th17 cells, BATF is neither sufficient nor required for accessibility at the Il9 locus. Here we show that STAT5 is the earliest factor binding and remodeling the Il9 locus to allow BATF binding in both mouse and human Th9 cultures. The ability of STAT5 to mediate accessibility for BATF is observed in other Th lineages and allows acquisition of the IL-9-secreting phenotype. STAT5 and BATF convert Th17 cells into cells that mediate IL-9-dependent effects in allergic airway inflammation and anti-tumor immunity. Thus, BATF requires the STAT5 signal to mediate plasticity at the Il9 locus.

Date: 2020
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DOI: 10.1038/s41467-020-18648-6

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