title: IL-9 is a Th17-derived cytokine that limits pathogenic activity in organ-specific autoimmune disease.
abstract: IL-9 is a pleiotropic cytokine with key functions in tolerance and inflammation, and its expression is considered a hallmark of Th2-lineage cells. Here, we report that human and mouse Th17 cells are a significant source of IL-9. The expression of IL-9 by Th17 cells was strictly dependent on the presence of TGF-β and IL-1β, and inhibited by IL-4. IL-9-deficient Th17 cells induced more severe autoimmune gastritis following transfer to nu/nu recipient mice. Th17 cells did not appear to be the target of IL-9 bioactivity as Th17 expansion and differentiation was comparable using IL-9-deficient CD4(+) cells or when IL-9 was neutralized with antibodies in vitro. However, reduced mast cell activity was associated with the increased pathogenicity of IL-9-deficient Th17 cells. Together, these results demonstrate a previously unappreciated role for IL-9 in dampening the pathogenic activities of Th17 cells.
authors.affiliation: Respiratory, Inflammation and Autoimmune Diseases Research, MedImmune, LLC, Gaithersburg, MD, USA. stephensg@medimmune.com
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Stephens
authors.forename: Bonnie
authors.initials: B
authors.lastname: Swerdlow
authors.forename: Ebony
authors.initials: E
authors.lastname: Benjamin
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Alison
authors.initials: A
authors.lastname: Humbles
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.forename: Michael
authors.initials: M
authors.lastname: Fung
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D005756:Gastritis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D016906:Interleukin-9 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: C508607:IL9 protein, human; D016906:Interleukin-9