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

• Published in: Nature communications Vol. 11; no. 1; p. 4882
• Main Authors: Fu, Yongyao, Wang, Jocelyn, Panangipalli, Gayathri, Ulrich, Benjamin J., Koh, Byunghee, Xu, Chengxian, Kharwadkar, Rakshin, Chu, Xiaona, Wang, Yue, Gao, Hongyu, Wu, Wenting, Sun, Jie, Tepper, Robert S., Zhou, Baohua, Janga, Sarath Chandra, Yang, Kai, Kaplan, Mark H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.09.2020; Nature Portfolio
• Subjects: 13; 13/31; 38; 38/15; 631/250/127/1213; 631/250/2502/2170; 64; 64/60; 96; 96/21; 96/31; Animals; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - immunology; Cell Differentiation; Female; Humanities and Social Sciences; Humans; Interleukin-9 - genetics; Interleukin-9 - immunology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Science; Science (multidisciplinary); STAT5 Transcription Factor - genetics; STAT5 Transcription Factor - immunology; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology; Th17 Cells - immunology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18648-6

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. BATF is a transcription factor that is needed for IL-9 production by T helper 9 cells. Here the authors show that STAT5 is needed at the Il9 locus to enable BATF to function in this manner and that this interaction can reprogram other T helper subsets into IL-9 producing cells, thus regulating the immune response to disease.