title: Th17 cells demonstrate stable cytokine production in a proallergic environment.
abstract: Th17 cells are critical for the clearance of extracellular bacteria and fungi, but also contribute to the pathology of autoimmune diseases and allergic inflammation. After exposure to an appropriate cytokine environment, Th17 cells can acquire a Th1-like phenotype, but less is known about their ability to adopt Th2 and Th9 effector programs. To explore this in more detail, we used an IL-17F lineage tracer mouse strain that allows tracking of cells that formerly expressed IL-17F. In vitro-derived Th17 cells adopted signature cytokine and transcription factor expression when cultured under Th1-, Th2-, or Th9-polarizing conditions. In contrast, using two models of allergic airway disease, Th17 cells from the lungs of diseased mice did not adopt Th1, Th2, or Th9 effector programs, but remained stable IL-17 secretors. Although in vitro-derived Th17 cells expressed IL-4Rα, those induced in vivo during allergic airway disease did not, possibly rendering them unresponsive to IL-4-induced signals. However, in vitro-derived, Ag-specific Th17 cells transferred in vivo to OVA and aluminum hydroxide-sensitized mice also maintained IL-17 secretion and did not produce alternative cytokines upon subsequent OVA challenge. Thus, although Th17 cells can adopt new phenotypes in response to some inflammatory environments, our data suggest that in allergic inflammation, Th17 cells are comparatively stable and retain the potential to produce IL-17. This might reflect a cytokine environment that promotes Th17 stability, and allow a broader immune response at tissue barriers that are susceptible to allergic inflammation.
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN 46202; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; and.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glosson-Byers
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN 46202;
authors.forename: Sarita
authors.initials: S
authors.lastname: Sehra
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN 46202; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; and.
authors.forename: Gretta L
authors.initials: GL
authors.lastname: Stritesky
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN 46202;
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN 46202; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; and.
authors.forename: Olufolakemi
authors.initials: O
authors.lastname: Awe
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN 46202; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; and.
authors.forename: Duy
authors.initials: D
authors.lastname: Pham
authors.affiliation: Department of Biology, Ball State University, Muncie, IN 47306.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Bruns
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN 46202; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202; and mkaplan2@iupui.edu.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
mesh_terms: D000536:Aluminum Hydroxide / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D006967:Hypersensitivity / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D000536:Aluminum Hydroxide; D016207:Cytokines; D020381:Interleukin-17; D010047:Ovalbumin; D011956:Receptors, Cell Surface; C515932:Il17f protein, mouse; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit
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