title: Etv5 Regulates IL-10 Production in Th Cells.
abstract: IL-10 is an immunoregulatory cytokine that has broad effects across the immune system. In Th cell subsets, Th2 cells produce considerable amounts of IL-10. The transcription factors that regulate IL-10 production in Th2 cells are still incompletely described. In this study, we demonstrate that the ETS family transcription factor ETS variant (Etv)5 regulates IL-10 production in Th2 cells. T cell-specific Etv5-deficient and littermate control mice demonstrated that IL-10 production and gene expression were significantly decreased in the absence of Etv5. In anAspergillus fumigatusextract-induced inflammation model, IL-10-producing CD4+T cells in bronchoalveolar lavage and lung were significantly decreased in mice that lacked Etv5 in T cells, compared with control mice. We showed that Etv5 directly binds to theIl10locus conserved noncoding sequence 3 site and that it activates gene expression in a luciferase reporter assay and following retroviral transduction. Etv5 deficiency did not affect the expression of other transcription factors known to be important for expression of IL-10, including Jun family members, GATA3, E4BP4, and IFN regulatory factor 4. However, in the absence of Etv5, binding of these transcription factors to theIl10locus was dramatically reduced. Ectopic Etv5 expression in Th2 cells that lack Etv5 restored IL-10 production and the binding of IL-10-inducing transcription factors including E4BP4, IFN regulatory factor 4, and GATA3. Taken together, we conclude that Etv5 plays a crucial role in regulating IL-10 production in Th2 cells by facilitating the binding of IL-10-inducing transcription factors at theIl10locus.
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; and.
authors.forename: Byunghee
authors.identifier: 0000-0003-3554-4449
authors.initials: B
authors.lastname: Koh
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Hufford
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202; mkaplan2@iupui.edu.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; and.
authors.forename: Mark H
authors.identifier: 0000-0002-2923-8245
authors.initials: MH
authors.lastname: Kaplan
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006967:Hypersensitivity / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000485:Allergens; D000946:Antigens, Fungal; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; C497441:Nfil3 protein, mouse; D014157:Transcription Factors; D016753:Interleukin-10