title: IL-9 promotes Th17 cell migration into the central nervous system via CC chemokine ligand-20 produced by astrocytes.
abstract: Newly discovered IL-9-producing helper T cells (Th9) reportedly exert both aggravating and suppressive roles on experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. However, it is still unclear whether Th9 is a distinct Th cell subset and how IL-9 functions in the CNS. In this study, we show that IL-9 is produced by naive CD4(+) T cells that were stimulated with anti-CD3 and anti-CD28 Abs under the conditions of Th2-, inducible regulatory T cell-, Th17-, and Th9-polarizing conditions and that IL-9 production is significantly suppressed in the absence of IL-4, suggesting that IL-4 is critical for the induction of IL-9 by each producing cell. The IL-9 receptor complex, IL-9R and IL-2Rγ, is constitutively expressed on astrocytes. IL-9 induces astrocytes to produce CCL-20 but not other chemokines, including CCL-2, CCL-3, and CXCL-2 by astrocytes. The conditioned medium of IL-9-stimulated astrocytes induces Th17 cell migration in vitro, which is cancelled by adding anti-CCL-20 neutralizing Abs. Treating with anti-IL-9 neutralizing Abs attenuates experimental autoimmune encephalomyelitis, decreases the number of infiltrating Th17 cells, and reduces CCL-20 expression in astrocytes. These results suggest that IL-9 is produced by several Th cell subsets in the presence of IL-4 and induces CCL-20 production by astrocytes to induce the migration of Th17 cells into the CNS.
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sonobe
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Akahori
authors.forename: Shijie
authors.initials: S
authors.lastname: Jin
authors.forename: Jun
authors.initials: J
authors.lastname: Kawanokuchi
authors.forename: Mariko
authors.initials: M
authors.lastname: Noda
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Akio
authors.initials: A
authors.lastname: Suzumura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016906:Interleukin-9 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D017077:Culture Media, Conditioned; D016906:Interleukin-9; D015847:Interleukin-4