title: Regulation of human Th9 differentiation by type I interferons and IL-21.
abstract: Interleukin (IL)-9-producing CD4(+) T cells are a novel subset of T helper (Th) cells that develops independently of the Th1, Th2, Th17 and regulatory T-cell lineages. Similar to the murine model, transforming growth factor (TGF)-beta and IL-4 directed human naive CD4(+) T cells to produce IL-9. Whereas IL-4 suppressed TGF-beta-induced Foxp3 expression, TGF-beta failed to inhibit IL-4-mediated upregulation of the Th2 transcription factor GATA-3. Addition of IL-1 beta, IL-6, IL-10, interferon (IFN)-alpha, IFN-beta or IL-21 to Th9-polarizing conditions augmented Th9 differentiation, while the Th1-associated cytokines IFN-gamma and IL-27 partially suppressed IL-9 production. Given that T cells are a primary source of IL-21, IL-21 expression was analyzed under Th9-polarizing conditions in the context of inflammatory cytokines. Surprisingly, type I IFNs induced elevated levels of IL-21, and blockade of IL-21 abrogated their ability to enhance Th9 differentiation. Taken together, these data indicate a complex cytokine network in the regulation of human IL-9-producing CD4(+) T cells.
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. yekimwg@stanford.edu
authors.forename: Michael T
authors.initials: MT
authors.lastname: Wong
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Ye
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alonso
authors.forename: Angela
authors.initials: A
authors.lastname: Landrigan
authors.forename: Regina K
authors.initials: RK
authors.lastname: Cheung
authors.forename: Edgar
authors.initials: E
authors.lastname: Engleman
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Utz
mesh_terms: D019138:Antibodies, Blocking / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D058408:Th1-Th2 Balance; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D000098546:Interleukin-21
chemical_list: D019138:Antibodies, Blocking; D007370:Interferon Type I; D016906:Interleukin-9; D007378:Interleukins; D016212:Transforming Growth Factor beta; D000098546:Interleukin-21