title: The ETS Family Transcription Factors Etv5 and PU.1 Function in Parallel To Promote Th9 Cell Development.
abstract: The IL-9-secreting Th9 subset of CD4 Th cells develop in response to an environment containing IL-4 and TGF-β, promoting allergic disease, autoimmunity, and resistance to pathogens. We previously identified a requirement for the ETS family transcription factor PU.1 in Th9 development. In this report, we demonstrate that the ETS transcription factor ETS variant 5 (ETV5) promotes IL-9 production in Th9 cells by binding and recruiting histone acetyltransferases to the Il9 locus at sites distinct from PU.1. In cells that are deficient in both PU.1 and ETV5 there is lower IL-9 production than in cells lacking either factor alone. In vivo loss of PU.1 and ETV5 in T cells results in distinct effects on allergic inflammation in the lung, suggesting that these factors function in parallel. Together, these data define a role for ETV5 in Th9 development and extend the paradigm of related transcription factors having complementary functions during differentiation.
authors: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202;
authors: Byunghee
authors: 0000-0003-3554-4449
authors: B
authors: Koh
authors: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202;
authors: Matthew M
authors: MM
authors: Hufford
authors: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202;
authors: Duy
authors: D
authors: Pham
authors: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202;
authors: Matthew R
authors: MR
authors: Olson
authors: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202; and.
authors: Tong
authors: 0000-0002-1152-3128
authors: T
authors: Wu
authors: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202;
authors: Rukhsana
authors: 0000-0002-0097-2622
authors: R
authors: Jabeen
authors: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706.
authors: Xin
authors: X
authors: Sun
authors: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; mkaplan2@iupui.edu.
authors: Mark H
authors: 0000-0002-2923-8245
authors: MH
authors: Kaplan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D016906:Interleukin-9 / Q000096:biosynthesis / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000502:physiology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D004268:DNA-Binding Proteins; D016906:Interleukin-9; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C513242:Etv5 protein, mouse